auto immune disease diagnosis but unsure which one

[buddy’s mum]

Hi
I'm new to the site and would appreciate any advice.
Buddy is 7 year old cavoodle- his mother was a cavoodle and his dad a poodle.
Last vaccinated April 17. Weighed 7.7kg at start.
Eats home cooked food and some shop bought dry food.
Has an underbite and has a dental clean once a year. Last done December 17.

Had reaction to worming drops late 2017 and they had to be wiped off.  This disrupted his schedule. Changed to heart worm tablets.
Was clipped on 13 April
He is an indoor dog.
Over a few week I noticed some subtle changes in behaviour- would hide away under desk after eating. Normally did this when he had done something naughty  like paw licking or when I want to bath him. Exercise  tolerance good- happy to do 4km walk. Did this the day before I took him to the vet.  Was sleeping in a bit and also not as social. I noticed a decreased water consumption for 3 days.  Stool normal and urinating ok.  Tended to rub face on carpet after eating . Had one episode of gagging/ retching in week before illness.

21 May 2018 Vet examined him and said it may be a viral infection and to observe him.  He had a slightly low lymphocyte count. Rest of bloods including liver and renal function normal.  Lymph glands not remarkable.

On evening if 22 May I noticed that he had a large submandibular lump on right side. I took him back to vet and she felt many of his lymph nodes were bigger. She took FNAs  of the lymph nodes. The right side submandibular area was very swollen compared to left. Not tender and not an abscess. I was told he may have lymphoma and to wait for the results.

Evening of 23 May dog was very lethargic and weak- only wanted to lie in basket and not on floor. I decided to take him to another vet. He was eating but not drinking. Vet concerned about right large submandibular node. Plan was to check pharynx and oesophagus for any lesions and X-rays. Also to take biopsies of lymph nodes

Vet  ultrasounded mass- oedematous swelling around slightly enlarged lymph node.When she spoke to me she told me it wasn't quite like normal cellulitis and not an abscess.  Chest and oral X-rays normal. Oesophagoscopy and gastroscope normal.

Slides  of biopsy which came back a few days later-no evidence of lymphoma. popliteal and submandibular nodes no obvious effacement of node
Plasma cells present
Moderately Increased macrophages and eosinophils In sinuses of both popliteal and submandibular node. 

Kept overnight hydrated and picked up next day. On amoxyclav 125mg twice a day. Three week course.

On 31 May returned -submandibular mass decreased. Localised dermatitis medial aspect left foreleg.- possible hot spot.

I made bone marrow broth and he drank this and eventually started drinking water again. Had diarrhoea from antibiotic and went on to develop anal gland abscess - never had problems before- which ruptured on grass outside vet while passing stool.  1  June

Revisit 8 June. Buddy's improvement generally was slow in that he wasn't himself and was more lethargic and sleepy than normal. Also didn't seem as steady as normal and not jumping up on high things. Eating and drinking ok.

Thought this may be due to antibiotics and loose stool causing him to feel a bit out of sorts

Took 3 week course. Stopped antibiotics and he slowly returned to his former self.


Probably lasted a few weeks before he was not quite as active as usual. Still active but not himself. Rubbed and scratched his right ear only occasionally - looked fine inside - really only after eating. I noticed he started  rubbing the top of his head on carpet occasionally after eating as well as both ears and mouth. he went off water again. His breath was really bad but it seemed to come deeper than from his teeth. He would yawn and then it would appear to catch as if it was sore. Yawned more than normal.  Bark not quite normal- higher pitched. Not vocalising as much. Buddy had exaggerated swallow when eating. No retching. No problem chewing chicken.

25 July returned to Vet. Buddy had temperature of 39.8
Had mild neutrophilia and increased globulins
Admitted for 2 nights then taken home on amoxyclav. Breath quickly smelled better.  Returned for blood test on 28 July - neutrophils from 13.36 to 13.29.  Temperature 38.4. Vet not happy and changed to Baytril.

On Monday 30 July returned as not drinking. Buddy admitted. Plan to check mouth and perform dental clean.
Neutrophils up even further 17.47. Globulins raised - no evidence of renal or liver issues.
Teeth cleaned but gums fine- no gingivitis. Tonsils ok - possible mild inflammation of larynx. I believe there was some mucus present as well. Swabs taken
Put back on noroclav
He was discharged on Noroclav 125mg
Xrays of chest normal and compared to previous X-ray.

Actinomyces was cultured in throat - found normally in dogs? Vet asked buddy to be admitted on 3 August
Given penicillin high doses iv for actinomyces on 3 August 4 August 5 August
No improvement- actually got worse. Another vet working on Sunday noted he was stiff and had pain in right rear leg. Couldn't repeat the pain reaction though.
Changed to triple therapy amoxyclav, baytril and metronidazole

Clinically and bloods worse so on Wednesday 8 August metronidazole changed to clindamycin. He looked a little brighter on 10 August and temperature down. Vocalised and managed to make a decent barking sound- not done that for a while! Took him to park near vets and after eating he tried to rub his ears - especially right and also top of head on ground. 11 August bright in morning not quite as bright in evening.
12 August morning quite bright but temperature down. On walk near vets managed to climb 3 stairs. Discharged 12 August but temp of 39.4. Measured later at home 39.6. During 10 days in hospital on iv fluids continuously Buddy not keen to drink but would eat.
Given amoxyclav clindamycin and baytril at home
13 August  temp 39.6. He started walking like an old dog and appeared stiff. Right hind leg appeared tender when I first touched it. Couldn't repeat that though. Occasional fast breathing and panting. Vet felt it may be fluid but this panting continued on and off till 15 August.
14 August temperature still up, went to see Vet. Buddy not drinking still and very lethargic. I was giving him water by syringe. He was eating though. Bloods showed that his neutrophils up even further - 25.96 on 11 August to 29.09 on 14 August.
Vet mentioned mri and csf tap. Buddy unable to get up from lying position and unable to lie down from upright position. Muscles very wasted- down to 6.2kg. I was having to move him in his basket and change his position as he couldn't do it. I carried him out to wee and poo. Didn't walk more than 2 steps. Refused food on 14 August and morning of 15. Decided not to go ahead with more tests as he was suffering- tests would involve a 6 hour round trip in car.

On 15 August vet put him on steroid 2mg/ kg twice a day- total of 4mg/kg. after 8 hours remarkable as could actually get up out of bed to drink. Was walking  around less stiffly. Still very tired but more alert. Stopped antibiotics

Drank lots on 15 and morning of 16 August  then stopped.
Exaggerated swallow never totally went away. Seemed difficult to swallow. Ate some wet royal canin to which I was advised to add water and appeared to choke. Stopped royal canin and back on chicken. Bad side effects from steroids - appeared restless and uncomfortable- panting and awake a lot.  Breathing very fast.

Went to specialist vet on 20 August given remarkable recovery. Nothing obvious on hour long  examination. Told to stop steroids and return when he's worse. Retuned 4 days later. Another full hour examination but no localising symptoms. Still refusing to drink. Eating well.  Specialist Vet couldn't offer any more general tests- asked about Creatinine kinase but vet felt not worth while. Offered an abdominal ultrasound but told it was unlikely to find anything as his blood results normal and no abdominal symptoms. No lymphadenopathy peripherally. With nothing to go on not worth subjecting him to joint and csf taps and muscle biopsies. Most likely auto immune but may be underlying infection or cancer.

Given 2mg/kg per day of prednisolone and told to taper to 1.75mg/kg after 10 days.
Buddy has improved remarkably. I spoke to Specialist vet on Friday and his dose has been adjusted from 2 mg/kg - 12.5 mg daily down to 10 mg daily for at least 2 weeks. Then will be dropped stepwise by about 25% every 3-4 weeks.

He's still reluctant to drink and I'm giving him chicken stock and water jelly. He is eating mainly chicken with a few veggies- I've added natural health booster to his food to add some vitamins.  He is walking every day and is more confident going up and down stairs. He  struggles to jump up high - he has been more successful in the last 2 days compared to a week ago. He's gone from 6kg to 6.5 kg but his muscles are very wasted. I've raised his bowl to ensure that it's easier to swallow.  No evidence on X-ray of megaoesophagus but I'm thinking his exaggerated swallow and his reluctance to drink water may be a functional issue. Eating very well and very hungry all the time! His bark has improved but is higher pitched than before. He still seems to catch when he yawns. He's stopped the panting and licking of his lips which in retrospect I think were signs of pain.  He is still occasionally scratching at his right ear and occasionally rubs his ears and top of head on floor after eating. After which he sometimes lies on his back and gives that a rub. 

I'm enjoying his company on a day to day basis as I'm aware that without a diagnosis his prognosis is uncertain. However the steroids are working for now and Buddy is happy and sleeping well at night.

Has anyone seen anything similar? Not sure if the significance of the right ear scratching and the rubbing of top of his head. No external ear infection according to vet. Seems to mainly happen after eating but not every time. Remarkable response to steroids with 6-8 hours. Is this normal response- does it help point to a diagnosis? I'm thinking polymyositis but I've got nothing to go on. Possible polyarthritis - His joints were examined by two specialist vets and an orthopaedic vet and there was no evidence of pain or fluid. No obvious central nervous system signs on examination! Any ideas would be appreciated
Thanks

[Jo CIMDA]

Hi and welcome

Gosh what an eventful time you and Buddy have had.

I am so pleased he is responding well to the steroids.  Yes, with certain AI diseases the quick response to immunosuppressive steroid treatment is typical and this allows for a presumptive diagnosis of polymyositis to be made.  To obtain a definitive diagnosis of IM polymyositis several muscle biopsies would have to have been taken and analysed.  To definitively diagnose IM polyarthritis synovial fluid from the joints have to be drawn and analysed.  A definitive diagnosis is not always necessary, or possible, and therefore starting immunosuppressive treatment is the right way to go for Buddy. 

The symptoms you describe are very familiar to me.  I had a boy who was eventually diagnosed with immune mediated masticatory myositis,  which developed into generalised polymyositis and polyarthritis.  The different high pitch bark, reluctance to drink/eat, severe pain and inability to move as a result of the pain, severe muscle loss etc.,  is all familiar.  The rubbing of ears I would suggest is likely to be in an attempt to relieve the pain or discomfort.

The symptoms you describe are very typical, and although megaoesophagus has not been detected on the X-ray, it is unlikely, given the length of time before immunosuppressive doses of steroids were given, that the muscles in Buddy's throat would not be affected even in a mild way.  Feeding him on a raised platform is a good idea and it might avoid any choking complications or aspirate pneumonia.  If Buddy does have a degree of Mega-O then this will not change but the good news is with polymyositis after a good immunosuppressive drug protocol his muscles can be gradually built up again and he will be pain free.

Buddy is now on the correct immunosuppressive dose of 1mg/kg/12hours.  As long as the side effects allow I wouldn't be in a hurry to reduce this dose and if you can stretch the duration to at least 21 days then that gives a better chance of achieving long term remission. See the Michael J Day protocol below.  It is the best protocol I have come across and it can be confidently used as a guide.  Prof Day is among the world's top veterinary immunologists.   If you lower the dose of steroids too soon then a relapse is very possible and then you will have to raise the dose of steroids back to an immunosuppressive  dose and start all over again.  You may even have to introduce another 'combination' drug to give added immunosuppression and because the steroid side effects you may have to lower the steroids sooner than usual. 

Buddy should be on something to protect his stomach such as omeprazole or ranitidine. If he isn't then ask your vet about this.

From now on aim to keep Buddy as natural as possible and avoid any unnecessary spot-on treatment, preventative worming etc., and vaccines.

Buddy is responding well to the steroids and this means that it is the correct treatment form him.  The dose and duration of treatment is crucial to the outcome but I am hoping that Buddy will achieve long term remission and have a good life.  Eventually I hope he will be drug free or at least on a low every other day dose of steroids to keep him stable. 

Jo



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.


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.

[buddy’s mum]

Thank you so much for your reply! It is a relief to hear that Buddy's symptoms make sense. I have been concerned by his bark and his swallowing but was told initially it was because he had a throat infection and even the specialist vets weren't over interested in these symptoms. On googling his symptoms I came across polymyositis. This wasn't even given to me as a differential but it makes more sense than a MUO or polyarthritis. As Buddy wasn't drooling or vomiting my concern regarding megaoesophagus was dismissed.  I was also told as his heart rate wasn't very high he wasn't in pain! He doesn't complain or whimper which was to his disadvantage and in the ten days he was in hospital he just wasted away. I got the impression they thought I was overreacting when I said Buddy was in pain.
Buddy is not on a gastroprotectant.
Ompeprazole only comes in 10mg tablets- can I halve the tablets as the dose is 1mg/kg for dogs? Which is better- ranitidine, famotidine or omeprazole? My initial vet gave me ranitidine with the antibiotics but it was a 150mg tablet and I was told to give Buddy a quarter- this equates to 37.5 mg and I believe his dose would be 12.5mg twice a day.  When I mentioned this I was told to give him a sliver of tablet with the antibiotics. Not sure how accurate a sliver would be! Do you think I should do this? I could get some famotidine  20 mg and divide that into 4- he would then get a dose of just under 1mg/kg. I started reducing  the dose from 12.5 to 10 today- at per the specialist vets instructions-  but I will go back to 12.5 tomorrow for a total of 21 days as I would rather err on the side of caution. He's only been in the dose for 11 days so far!
Your support and help is much appreciated!

[Jo CIMDA]

HI

Dogs can be very stoical even when they are in extreme pain some don't complain they just become quite and reluctant to move.   Clearly the treatment Buddy is having is correct, so that is great news, and you can be hopeful that this will bring him into remission, but relapses are not uncommon and this is why it is best, if at all possible and the side effects of the drugs allow, to get the drug protocol right first time.  Below are some references for you to study.


FYI
The dose of

Omeprazole is:  Dogs: 0.5 - 1mg/kg/once daily (Plumb's Veterinary Drug Handbook, Eighth edition and BSAVA Small Animal Formulary, 6th Edition)      I wouldn't split the tablet or break a capsule.   In the UK this is a prescription only drug.

Ranitidine: Dogs: 2mg/kg/8-12 hours (BSAVA Small Animal Formulary, 6th Edition) 

or  Ranitidine:  Dogs:  1-2mg/kg 8-12 hours (Plumb's Veterinary Drug Handbook Eighth Edition)

Ranitidine can be bought cheaply from the supermarket or the chemist and is usually labelled 'Indigestion tablets - Ranitidine 75mg. It is the generic form of Zantac

Famotidine:  Dogs and Cats:  0.5 - 1.0 mg/kg/12-24 hours (BSAVA Small Animal Formulary, 6th Edition)

Famotidine: Dogs: 0.5 - 1.1mg/kg 12-24 hours (Plumb's Veterinary Drug Handbook Eighth Edition)

Which one to use may depend on what you can buy and also the dose of tablet available,  and how you can split the dose correctly.  As Buddy is a small dog I feel Ranitidine would be the best as you can quarter a 75mg tablet and this would give you a dose of 18.75mg.  This is slightly over the 2mg/kg/8hours so you can just give it twice a day.  Ranitidine  is available in liquid form too and this might be easier to administer.   

Ranitidine has a wide safety margin.   
See this link: 
https://www.wedgewoodpetrx.com/learning-center/professional-monographs/ranitidine-for-veterinary-use.html

Jo

[buddy’s mum]

Thanks so much. One further question - buddy has been prescribed a single daily dose of prednisolone - should I be rather splitting the dose into two as per the protocol? Will that be safer?
Your advice is much appreciated!

[Jo CIMDA]

Hi

A single dose of prednisolone given in the morning is said to be ideal because that is the time when the body's own cortisol production is at its highest and therefore it mimics the natural hormone cycle. In reality, an immunosuppressive dose of prednisolone is nowhere near the same dose as naturally occurring cortisol so while the dog is on very high doses of prednisolone, and at risk of some serious side effects, in my opinion the risks of once a day dosing outweigh the benefits.  When a dog gets down to a much lower daily dose of prednisolone then giving a single dose in the morning is advisable and certainly mimics the natural cortisol production. 

Having said that, smaller dogs can tolerate prednisolone much better than larger ones so giving the 24 hour dose of prednisolone in one go may be OK for Buddy but the side effects of prednisolone are significant, and to be expected, and by dividing the daily dose of 2mg/kg/24 hour into two and giving it every 12 hours you can reduce the side effects of the drug, and in particular the gastric side effects, and therefore the tolerance of the drug is increased.

Dividing the daily dose does not reduce efficacy because the biological half life of prednisolone is 12-36 hours so once you have started therapy the biological action is ongoing as long as the same dose is given every 12 hours. Sometimes a higher loading dose is given for the first 48 hours and then it is reduced to 1mg/kg/12hours. 

I hope this information helps.

Jo