Need Some Advice Please

[Arinashdad]

I have joined a couple of sites on FB and have gotten some great advice.  Karen Sexton with IMHA Dogs-Support Group suggested I reach out to Jo, the Administrator and others for additional advice on this forum.

Here is our case:
I have a 7.5 year spayed English Bulldog (Puddles) that was diagnosed with IMHA on 12-13-17  prior to this she was in perfect health other than a TPLO surgery in September 2016, made a full recovery.  Since diagnosed on 12-13-17 she as been on 50mg of prednisone.  We give her 25mg in the morning and 25mg at night, she has gained some weight and is about 54 pounds.  She has never been overly active but is stirring about more now then before being diagnosed and gums are as pink as our other bulldog and chocolate lab.  We have noticed the impact on her muscles and her breathing has changed but the doctor said it was normal for the prednisone (owning 2 bulldogs you get obsessed with breathing and now the gums). 

She had massive diarrhea with the Atopica and Mycophenolate so the prednisone is the only thing she is on for suppression.  She is also taking the Omeprazole 20mg (twice daily and an hour before she eats and gets the meds), Clopidogrel 37.5mg (once daily) and Metronidazole 125mg (twice daily).  Originally the Vet had her Metronidazole at 250mg (twice daily) but I ran out of pills before they called in the prescription so I cut it in half and she did fine.  She has a strong appetite and hasn't had any nausea or diarrhea so I left her at the 125mg dose.  I am also giving her a 1200mg/360mg Omega-3 fish oil vitamin once daily and Milk Thistle Extract (500mg daily in 4 125mg doses throughout the day) and feeding her iron/protein food like eggs, meat and beef liver.

Historical PCV levels:
12-13-17 day of diagnosis PCV 17%
12-14-17 PCV 24% (2 hours post transfusion)
12-14-17 PCV dropped to 16%
12-14-17 PCV 24% (2 hours post transfusion also received IVIG)
12-14-17 PCV dropped to 17%
12-15-14 PCV 19%
12-16-17 PCV 20%
12-17-17  PCV 25%
12-18-17 PCV 25%
12-19-17 PCV 25% (released from hospital)
12-21-17 PCV 29%
12-23-17 PCV 29%
12-28-17 PCV 35%
1-15-18 PCV 36%

The doctor suggested we wait 2 weeks from the 1-15-18 test, retest and then to consider reducing the dosage.  On 1-16-17 she got a UTI and was put on 375mg of Amoxi trihudrate/Clavulanate (twice daily).  Her last dose will be the morning of 1-27-18 and according to the Vet we would need to wait one week after she finishes the meds before retesting her and starting the reduction.  The UTI doesn't push the retesting date out only a couple of days however I want to start reducing her now if we can.  The doctor said I could do what I wanted to do but it was against her professional opinion and medically wouldn't suggest reducing until retesting.   

Finally my question.... I want to go ahead and start reducing her prednisone and if it would benefit her go ahead and cut out the Metronidazole completely.  I have never been a fan of medications but know it's the necessary evil in this case.  Please let me know your thoughts and thank you in advance.  I apologize about the lengthy post but wanted to include as much information as I could. 

[Jo CIMDA]

Hi and welcome

I am sorry Puddles has IMHA.  She has done extremely well to have a PCV of 36%

Puddles weighs 24.54kg, so she has been on the correct dose of prednisolone and it has done it's job well.  It just goes to show that prednisolone can bring inflammatory AI disease under control without other immunosuppressive drugs.  Sometimes, of course, other drugs are necessary but just because they are available doesn't mean that the old tried and tested ones, like prednisolone,  are no longer effective.  This is great news for Puddles.

Having praised the virtues of prednisolone, it is knowing when to reduce the dose that is equally important to the control of the disease, the side effects, and ultimately achieving remission.

UTI's are common place when a dog is on immunosuppressive doses of prednisolone.  This is because the immune system is so suppressed it cannot fight bacteria.  Given her good PCV, I am surprised the preds weren't lowered at the time of the UTI diagnosis. The diarrhoea may also have been a spin off of immunosuppression caused by the preds.  The metronidazole seems to have done it's job and I do wonder as she is now back to normal why she is still needing it?

Prednisolone impacts on every part of the body and noticeably in a dog, laboured breathing and muscle weakness is common place and to a certain extend to be expected, however, there sometimes comes a point where these signs become more significant and it can be an indication of intolerable side effects and this needs to be addressed.  I cannot tell (because I cannot see Puddles) how one would classify Puddles current clinical signs but if you think the preds are having a greater effect on her breathing and muscle weakness than is acceptable then the preds need to be lowered before the problems becomes acute.

Puddles has been on an immunosuppressive dose of preds for nearly 6 weeks.  The recommended, average time is up to 28 days.  Once the preds have done their job there is no benefit in keeping the dose as it is and a good reducing prednisolone protocol should be used as a guide.  The best one I have come across is by Prof. Michael J Day.  He is among the top veterinary immunologists in the world, so it can be used with confidence, but always a reducing drug protocol has to be tailored to the individual taking into consideration the resolution of the disease and the clinical signs/adverse effects of the drugs.

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.

"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 decision to reduce the drugs has to be for you and your vet, but consideration has to be given to the fact that her vital organs etc., have to process all the drugs that you give, and therefore I agree with you when you say you want limit them.  Her bloods are really good and the antibiotics will hopefully rid her of the UTI, but if she remains on immunosuppressive preds for longer not only will the obvious adverse effects increase but she may get another UTI or skin infections etc.,  because her body is unable to fight bacteria while her immune system is being so suppressed.

I will post something about iatrogenic Cushing's syndrome to give you some idea of what is acceptable and what is unacceptable side effects of preds.

You seem very informed and are doing so much to help with diet and supplements etc.,  I would say to trust your instinct and believe that you know Puddles best - and try to get your vet to work with you on this.

Good luck.  You are over the worst.

Jo

[Jo CIMDA]

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.

[Arinashdad]

Thank you for all your help, you came highly recommended.  I have seen the reduction chart on various web sites and will probably start the reduction tonight.  I have read it is best to reduce the evening dosage first.  If I was to reduce the evening by only giving her half of a pill (10mg) and then the regular dosage (25mg) in the morning would this be acceptable? 

It is going to be impossible for me to get her blood tested before Monday but I don't want to wait that long before starting to reduce the amount.  When she was at the Vet 10 days ago they said everything looked fine.  I can see the muscle wasting, the thirst/urination and the pot belly/sagging back on her which isn't too bad because she has always been longer then the typical English Bulldog but regardless the signs are there.  My wife and I talked about it last night and see no other options.  I know we can't keep her on this high dosage much longer and if her PCV came back at 32% what options would we have at that point, we can't/I won't increase the amount.  If we start reducing according to the chart you provided tonight, monitor her closely through the weekend (we do this anyways) and have her blood tested on Monday or Tuesday wouldn't you think this might work.  And yes, I think I will also take her off the Metronidazole completely.

Thank you so much for all your help, you are a true blessing.
   

[Jo CIMDA]

Thank you for your kind words.   

Certainly reducing the evening pill is very acceptable.  Natural cortisol levels are at their highest in the morning and this is why they say more is gained from giving the dose in the morning as opposed to the evening.  The reason why the daily dose is split into two is to reduce the adverse effects, especially on the stomach, and make treatment more tolerable for the dog.

32% is a great place to be and I would expect this to rise as you lower the steroid dose.  Sometimes when a dog is at this level, and still on immunosuppressive dose of preds, the PCV doesn't rise but plateaus because prolonged, high doses of preds can cause bone marrow suppression.

At this stage more good can come out of reducing the preds than harm.  Because of her recent drug history, and the current signs of iatrogenic Cushing's, if the PCV started to decrease it wouldn't be wise to increase the dose of preds anyway and another immunosuppressive drug would have to be introduced.   

I think you will be surprised to see the difference a drop in preds will make to Puddles general wellbeing.

Jo

[Arinashdad]

We took her off the 1/4 tablet last night and this morning, so far all is well.  Her PCV was 36% last time that's why we were boggled that she wanted to wait another 2 weeks.  I couldn't agree more with her needing the reduction now.   Thank you again for all your help.