Questions about cyclosporine and azathioprine

[Koda bear]

Hi  I have a question regarding my 11 1/2 year old shep /pyr mix, Koda. He has recently been ill with GI upset, diagnosed with pancreatitis, with blood work and ultrasound findings.
It has been such a struggle with a diagnosis and I believe he has SLE, as the moderator here confirmed as well. Currently he is taking just 5mg per day, a small amount for a 40kg dog. But he is doing alright, still happy and hungry and able to walk around and enjoy life. Two new doctors say he has to get off the pred and probably does not have any immune disease! I had a very difficult discussion with one of them last night, who insists there is no immune problem with Koda.
He has lesions on his liver, but bloodwork all looked very good in September.

If if take him off I fear he will crash, just be totally unable to walk , and I will be losing him before the New Year. Pain killers do not help him at all, even high doses of opioids.  I will be talking with my own vet, today or tomorrow, who believes, somewhat, that he does have an immune disease. If I can convince her to try azathioprine, or cyclosporine, would that possibly help Koda at this late stage? With the hope that we can wean him off the pred in a few months. I know these drugs usually are started when the patient is at a higher pred dose.

And... we also are seeing a naturopathic vet, who is wonderful, wants to keep Koda at the 5 mg per day, and wants us to try Nrf2. (She can't believe that no one ever diagnosed SLE or put him on Azathioprine or cyclosporine earlier. She has not yet seen the results of the ultrasound though.)
Have you heard of this product,Nrf2? I have learned it has shown promising results with MS patients- people- ..?
So may vets, so disappointing and frustrating!!  Thank you so very much for any ideas to help our sweet Koda. I appreciate your time.
Missy

[Jo CIMDA]

Hi Missy

I haven't heard of Nrf2, so I am not able to comment.

5mg pred a day for a 40kg dog will not control an active, inflammatory autoimmune disease, especially one as debilitating as SLE, or stop a relapse if  an appropriate trigger is met, so in a way if there is a good reason why the 5mg pred a day should be stopped, for example if it is causing too much gastric acid or causing the pancreas to be overwhelmed leading to pancreatitis, then it could be withdrawn, or even weaned down over a period of a week or so and then stopped, which I think is better.  It is about getting a balance and evaluating the risk/benefit of the drug against the possible disease it may cause.  Pancreatitis is either chronic, which is manageable, or acute which can be life threatening.  It sounds as if Koda had chronic pancreatitis which is managed by a low fat diet.

Personally, if Koda is not showing the clinical signs of an active AI disease then I wouldn't start him on azathioprine or cyclosporine, both of which, have the capacity to cause pancreatitis or gastric upset. Using immunosuppressive drugs is not advised unless there is the need to significantly suppress the immune system to bring an inflammatory immune mediated disease under control.   These are not drugs that you would chose to use if you didn't have to.

There is no 'one' definitive diagnostic test for SLE.  It is usually diagnosed by the elimination of other AI diseases and various major or minor clinical signs. 



SLE - Systemic Lupus Erythematosus
SLE is a multisystemic disease that can affect many parts and systems of the body.  It is categorised into major and minor signs.
Major signs can be:
Shifting lameness (polyarthritis), anaemia and thrombocytopenia (blood abnormalities), skin lesions, kidney nephritis (inflammation)
Minor signs can be:
Inflammation of the heart, lungs & muscles, mouth ulcers, enlarged lymph nodes, gastrointestinal signs (vomiting and diarrhoea), central nervous system may be affected causing: Behavioural changes, seizures, and staggering (ataxia).

Clinical signs can be extremely varied and not all dogs with SLE will show the same symptoms. An antinuclear antibody blood test (ANA) can be useful in diagnosis but a negative result still does not rule out SLE.

Definite SLE:  (Reference: Canine Medicine and Therapeutics 4th Edition by Neil Gorman)
Positive ANA test, plus two major signs
positive ANA test, plus one major and two minor signs

Probable SLE:
Positive ANA test, and one major sign
Negative ANA test, and two major signs

The dog will normally demonstrate signs of pain and stiffness in the joints and this may be accompanied with anaemia, skin lesions and one or more of the minor signs.  One would expect the dog to show other clinical signs such as high temperature, enlarged lymph nodes, thrombocytopenia, lethargy, depression, lack of appetite, muscle weakness (myositis) sometimes causing weakness of the throat muscles (megaoesophagus).   Megaoesophagus is a serious complication and if this is present then the quicker correct treatment is started the more chance you have of limiting the effects.  A dog will have difficulty in drinking and eating and this can cause recurring aspirate pneumonia.  The primary autoimmune disease may have been brought under control but the effects of megaoesophagus may not resolve completely.
SLE can affect any body system/s. A definitive diagnosis may not be achieved, but it may be presumed, based on clinical evidence and response to treatment.  Again knowledge of breed predisposition and family history will be beneficial in obtaining a diagnosis.   Dogs can have periods of remission and relapse. 


Many autoimmune disease are treated speculatively because a definitive diagnosis can't be achieved, and if the immunosuppressive treatment works then one can assume it was an AI/IM disease.

A relapse can happen at any time when a dog is in remission if the dog encounters an appropriate trigger,.  Triggers are numerous and a particular trigger may induce an AI disease in one individual but not in another, so it is impossible to say which triggers Koda is vulnerable to, but if that trigger is met a 5mg of pred won't prevent an active AI disease occurring.

Some dogs do remain on a low dose of pred for life because when the dose was reduced a relapse occurred, but it is very likely that the dog was not in full remission to start with.  I had a dog with SLE and the lowest dose I could wean him down to was 15mg a day (he weighed about 23kg),  and even then, he would regularly relapse and I would have to raise the preds to an immunosuppressive dose and start weaning all over again. Incidentally, this boy died of acute pancreatitis.

It is not an easy decision to make, but I hope the above will give you more information to help with your decision.

Jo