Very Sick Boston Terrier - Please Help!

[mullintl]

My four year old Boston Terrier soul mate is very sick.  She has been supposedly battling an immune mediated disease leading to possible poly arthritis since early March 2018.  To shock and reset her immune system, she was prescribed 10mg of steroids that were tapered, starting March on 14th and ending on June 13th.  While on the prednisone, her fever was down, her appetite was up, and she seemed much peppier.  Upon finishing the prednisone, she slowly regressed back to her original symptoms of fever, lethargy and trouble standing along with some new developments such as drooling (only on her right side).   

Nori has completed an expensive series of tests over the past three month, all coming back normal or inconclusive.  We're looking at more tests, but it's all expensive guess work.  I'm hoping by detailing her symptoms, maybe we'll get lucky and some amazing reader will help us connect these dots.  We would be forever grateful for any shared experiences, suggestions, or AH HA moments that might help us find the cure for our baby.  Feel free to respond to this post or email me directly at: mullintl@gmail.com.

This little nugget sleeps in the bed under the covers.  I first noticed something was amiss on March 2nd when she refused to jump off the bed.  This was abnormal, but I attributed the behavior to her having a big day on the 1st, romping on the beach (we're in Charleston, SC) with her puppy pals. 

On the 3rd she appeared to be really tried, which again I thought might be the result of a big weekend.

On the 4th and 5th, she was lethargic and wasn't getting up to greet us when we got home. 

On the 6th, the lethargy was coupled with weakness and difficultly standing up (especially on her hind legs) so on the 7th we spend the entire day at the vet.  We learned that she had a very high fever.  The vet gave her fluids, an enroflxan injectable, performed a comprehensive blood chemistry panel and sent her home. 

He fever dropped and the blood chemistry came back normal, so Nori was diagnosed with a FUO (fever of unknown origins) and was prescribed Clavamox on March 8th. We also noticed some intermittent sniffing, coughing during this time.  The Clavamox didn't reduce her high fever, so on March 11th we stopped the Clavamox (125mg), started Doxycycline (100mg), and gave more fluids.  Our regular vet had was unable to perform additional testing and referred us to an internal medicine specialist.

On the 12th, the internist performed a comprehensive blood panel for vector borne disease (tick, flea, mosquito-based illnesses).  While we waited for the results, the lethargy continued with the lameness, but we did see a slight decrease in fever once the Doxy was started. 

On March 13th, Nori was given more fluids and had been vomiting.  The internist noticed swelling in her lymph nodes and was concerned about lymphoma, so we aspirated her lymph nodes and tested for cancer.  This test came back 'inconclusive' but the vet said lymphoma was unlikely.

On March 14th, Nori was prescribed 5mg of prednisone to treat for inflammatory disease.  She was also prescribed 16mg of cernia for nausea.  To date, her lethargy continued, along with milky, weepy, watery eyes, but her fever continued to drop.

On the 17th we stopped the cerenia for nausea.

On the 18th the blood test for vector borne disease came back negative from NC state, so we stopped the Doxycycline.  The internist said that at this point immune mediated disease was most likely. 

On the 20th, she was still tired and not herself, so she went back to the vet.  To recap, cancer was not noted and infection was not found, so immune mediated polyarthritis was suspected.  They upped her dose of prednisone to 5mg every 12 hours.

From March 20th – June 13th, she continued and tapered the prednisone.  Her fever was down, she was perkier (but never 100%).  She seemed to be doing significantly better when she was on the pred.  We certainly noticed a difference after the steroids were finished; she appeared much more lethargic, red eyes, licking paws, shaking. 

On June 19th we took her back to the internist.  Her temperature was normal and the vet noticed no pain.  Said she believed that the steroid worked as Nori no longer had a fever (even though she's still lethargic).  Suggested that perhaps the red eyes, shaking, lethargy was due to allergies resurfacing that may have been covered up by the steroids.  Suggested watching her for a little longer.

Today is Sunday, June 24th.  Nori's fever has returned.  She's constantly sleeping and clearly miserable.  I reached out to the breeder and asked if any other puppies had issues.  He is a farmer that only had one litter ever and said that he hasn't heard about the other litter mates so believes they are OK.  The male (Noris father) is a 12 year old outdoor farm dog that has never been to the vet.  The female, however, died at age 7.  He said one day they gave her a nexguard pro and the next day she was dead.  I don't know if this is relevant, but sharing anyways.

We are going back to the vet on Tuesday (or tomorrow if I can get an appointment).  We will be doing an ultrasound of her abdomen, radiographs of her chest and another blood chemistry.  Hopefully we are able to determine what's causing my little girl to be sick so that we can treat her.  We are nearing the end of the available testing, and I am nearing the end of my credit limit. 

I can't describe how much I love this dog. I'm choking back sobs as I list her symptoms here.  I'm not kidding when I said she's my soul mate.  She's literally my best friend.  If you have ANY suggestions, please please please share.  We need all the help we can get.

Thank you from the depth of my heart for taking the time to read this.

Sincerely,

Tessa

[Jo CIMDA]

Hi and Welcome

I am so sorry Nori has IMPA.  Well I presume this has been definitely diagnosed by joint taps.    Relapses of IMPA are not uncommon and the most likely time for a dog to relapse would be when the tablets are at a low dose.   I don't know how much Nori weighs so I can't say if the drug protocol she has been on is correct,  but  the Michael J Day protocol (copied below) is the best I know and it might be worth checking it against the one Nori was on initially. Prof Day is among the few top Veterinary Immunologists in the world. 

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.


I do not know what more you will discover by doing another load of tests and it might be better for her if you just start the immunosuppressive treatment again and assume a relapse.   If Nori responded well to the steroid the first time around then it is likely that she will respond again.  Check that she is on 1mg/kg/12 hours prednisolone (this is the recommended immunosuppressive dose) and if Nori were mine I would try this first and if it is a relapse of the IMPA then she should respond very quickly and you may even see that she is in much less pain within hours of giving the does - but the correct dose and for the correct duration of time is crucial to the outcome.  The prognosis for IMPA is really very good and if the drug protocol is correct Nori can achieve long term remission and most dogs are drug free.   

Also, make sure she is on something to protect her stomach from the excess acid that the steroids produce, so something like Ranitidine or omeprazole should be given  while she is on the steroids.  I presume as she is a Boston Terrier that she is on the small side, and this is a good thing when it comes to immunosuppressive treatment with prednisolone because smaller dogs cope much better with the side effects.   If she is not coping with the side effects of the drugs your vet may want to introduce another 'combination' drug such as leflunomide.

It is so upsetting, but it can and does get better, so be strong tomorrow when you see the vet and ask them why she has to have further tests and why she can't just start immunosuppressive treatment again when it is most likely she is having a relapse.

A tip -  Never be afraid to say you can't afford it because sometimes the vets want to do test after test when it is not necessary.

Jo

[Jo CIMDA]

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.

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.