IMPA & Addisons (Cushings)

[smp]

Am struggling with a potential IMPA diagnosis. Took my girl to an osteopath vet for arthritis, he thinks is IMPA because of her history.

Last fall our 9 yr old, 8.5kg Boston Terrier Keeley was diagnosed with Cushings. She'd probably had it for some time but not realized as she never drank/urinated more than normal, only had some hair loss and what our former long-term vet called black warts. Had LDDS, ACTH & few months discussing with vets, started on 10mg Vetoryl late Dec 2019. Her 10 day baseline check was ok (ACTH not available where we were). On Day 28 she stopped eating, vomited & started shaking. Knew these were Addison's signs & took her to an IMS immediately. Her ACTH that was >1,000 nmol/L to diagnose was now 9. She pent 3 days there and was given 5mg prednisolone & Fludrocortisone 100 ug, off for one week to redo her ACTH. It only increased to 14 nmol/L so she went back on prednisolone. We have redone her ACTH a couple of times to see if her adrenal glands would function on their own. Last test was 29 nmol/L so no. We are full-time travelers meaning we see multiple vets. One advised switching her from prednisolone to Cortineff because of the side effects of prednisolone. We've done this and she is doing very well, except for her arthritis. (1.5 tablet, split 2x/day)

She has had symptoms of arthritis for 3-4 years and received acupuncture and chiropractic treatments at our long-term vet. Because of her high cortisol, we never realized how bad it was. Post Addison's crisis, we've seen two vets who are osteopaths. The first did a cursory exam and x-rays, he passed us to a colleague (not sure if osteopath) who compared them to a set from 2019 and said arthritis. She's on gabapentin, we asked about other pain meds (Amantadine) but they wanted to try supplements first. We've tried supplements, gave theirs a go with no benefit. Had to switch vets, this osteopath did a more thorough clinical exam and said IMPA. He did not recommend joint taps to confirm, this was the first I've ever heard of IMPA so did not know to ask. He also did not take her temperature, at least not in front of us (she was out of our sight for a blood draw).

We need to change locations again, I have found a practice that does both endocrinology and osteopathy but wanted to ask about the IMPA diagnosis. Does this sound likely? She's been 'arthritic' for 3-4 years, has swollen wrists and walks stiffly but no one has ever mentioned a high temperature. She has never had an episode of not being able to stand. Her appetite is very good, she is interested in walking, being outside - she's not as energetic but she's also 10 now. Could she have been living with IMPA that long? I thought that it was more an acute disease. This last vet has us trying Flexadin Advanced and Neurovet alpha, if no change in a month then immunosuppressive therapy (hesitant because of her Addisons). I see some of the symptoms but struggle with others and that everything else she's had, she presents as a non-normal case.

Sorry for the long story, everytime we get close to resolving an issue, a new option arises.

Sheila

[Jo CIMDA]

Hi Sheila and welcome

I am sorry you are having these problems with your girl.

Hormone problems can be very confusing and they can also mask underlying conditions.

From what you have written, it is likely that if your girl had IMPA a few years ago it may have been masked when her body started to become Cushingoid,  because high cortisol naturally produce by the body will act the same as being prescribed high doses of prednisolone - which is an anti-inflammatory and used for the treatment of IMPA,  and the auto antibodies that cause IMPA would have been controlled by the naturally occurring high levels of cortisol.   If you remove the naturally occurring high cortisol (by the use of Vetoryl) then, if there is a predisposition to autoimmunity, the IMPA could be active again.

Another theory could be that the high cortisol naturally produced by the adrenal glands, resulting the diagnosis of Cushing's, could have depleted the body's calcium and this has caused osteoarthritis. I have had a dog with Cushing's and she developed severe arthritis as a result.   Vetoryl also took her levels of cortisol too low inducing a drug induced Addisonian crisis.

There is a huge difference between IMPA and osteoarthritis.  IMPA is an autoimmune disease that develops when the body's own immune cells attack the synovial fluid within the joints. It does not attack the structure of the bones. The treatment is immunosuppressive doses of prednisolone and then wean off the steroids over a period of 6 or more months in the hope that remission will be achieved.  The joints will feel hot and swollen to the touch and because it is an inflammatory AI disease a high temperature is always present.   

Even a low dose of Vetoryl can reduce cortisol levels too low to make the dog temporarily Addisonian.  If this happens the Vetoryl must be stopped to allow normal cortisol levels to increase.  After this event, over the following weeks you may see Cushing's symptoms return, and then it might be necessary to resume Vetoryl therapy.  Vetoryl also has the capacity to destroy the adrenal glands to the extent that glucocorticoid and mineralocorticoid hormones can no longer be produced by the adrenal glands and this induces permanent Addison's disease.  It is not common but it can happen.   

I think it is very important to ascertain whether the arthritis is osteoarthritis, rheumatoid arthritis or polyarthritis.  They are all treated differently.  It would be detrimental for a dog to be treated with high doses of steroids if it had osteoarthritis because this can make the condition worse.   You may have to have a joint tap performed to obtain a definitive diagnosis.

IMPA does not necessarily have an acute onset.  It can be progressive and over time (probably a few months or more) the joints will become more painful.

I had not heard of Cortineff, but I presume it is the same as Florinef.   It is a mineralocorticoid drug that is available in Europe.  As far as I can see it is a mineralocorticoid with a small amount of glucocorticoid.  If this is the case and your dog does have Addison's where both the mineralocorticoid and the glucocorticoid hormone is not being produced by the adrenal glands then it is a good idea to carry an emergency supply of prednisolone just in case she needs extra in times of stress.

Jo


IMPA - Immune Mediated Polyarthritis
Primary Immune mediated polyarthritis is the most common non-erosive polyarthritis in the dog. IMPA can be primary, or secondary to other diseases such as SLE, myositis or meningitis. Symptoms of IMPA can closely resemble Lyme disease or multiple joint infection and this has to be considered in the differential diagnoses.
For a confirmed diagnosis of IMPA, joint taps need to be performed to obtain evidence of infiltrating immune cells within the synovial fluid in the joints.   Clinical signs such as shifting lameness, soft tissue swelling around the joints, difficulty in rising to a stand, stiffness in the neck and back, and very high temperatures etc., can be vague and evident for several months prior to diagnosis.
Clinical signs therefore can be intermittent and initially antibiotic and non-steroidal anti-inflammatory drugs are usually given, but little improvement is seen. The disease continues to progress until the dog becomes quite overcome by the inflammatory process. Also, it is not unusual for the dog to become depressed and anorexic and stand with its head held low, unwilling to move. This is a very painful condition.

[smp]

Many thanks for the feedback, you've been able to clarify my spider web of thoughts.

I have been reading about the various conditions and understand we need to be certain before starting treatment...I am petrified of giving her the wrong medication. You've made me feel more comfortable that it could be IMPA. We have an appointment on Thursday at a specialist's practice that has both osteopath and IM vets, they have indicated they can do the joint taps within a couple of days. I also think she is feeling it in her neck, I noticed a couple of days ago that she acts as if it is stiff.

We stopped the Vetoryl the day she became sick, her Cushings symptoms have not returned. I talked to the IMS last week who treated her during the crisis and he feels she has permanent Addison's. (I'm very comfortable with his diagnosis, has PhD in Pathology from Texas A&M). Yes, Cortineff is the same as Florinef. We started her on prednisolone but she's actually done better on Cortineff. Giving booster doses of prednisolone is not something we've encountered yet, I first heard of this looking at the IMPA Facebook group. She's been on Fluoxetine so I need to read more about this & talk to the IMS.

Thank you again for such a thorough response. I know you are very busy and appreciate all of the time you've given me.

Sheila

[Jo CIMDA]

Hi Sheila

Additional prednisolone should be in your pocket just in case she encounters a stressful situation when you are out walking etc.  In a stressful situation, additional glucocorticoid supplementation is needed to cope with the stress.  Dogs without Addison's will automatically produce additional glucocorticoid by the adrenal glands to satisfy the flight/fight demand.   It is just a precaution.   

BTW, Addison's is easier to control with medication than Cushing's, so it isn't all bad.

Good luck on Thursday.

Jo