CIMDA

Jo I'm glad it's useful. I also put together this one about our learnings around prednisonehttps://shinyhappydoggy.com/side-effects-of-prednisone-in-dogs/ in case it's also helpful at all? All the things we wish we never had cause to learn, eh? 

Jo I just wanted to reach out here after I came across the (old) discussion of calcinosis. I documented my own dog's horrid experience with calcinosis circumscripta caused by prednisolone and wanted to make you aware of the article. I figure it might be helpful to others, particularly because it contains lots of pictures of the lumps and lesions in different stages of development. If you think it's worthwhile, please feel free to share it so we can keep raising awareness of all these things https://shinyhappydoggy.com/calcinosis-cutis-in-dogs/. I know we had a lot of trouble getting it diagnosed, so maybe this can help others get there faster in future. Cheers, and thanks as always, Jane

Catherine, I meant to say: we didn't get to the Canikur Pro paste but used slippery elm and now psyllium as well as Protexin probiotics. Stopped the probiotics for a week at the height of the diarrhea but have reintroduced to help rebuild gut biome. Do you use the Canikur pro paste regularly in a healthy dog or just when there's a problem? It does look like good stuff from the ingredients. Thank you so much for having been there for us. What do you think of this product, compared to Canikur? Have you used it? Is Canikur Pro preferable? : https://www.protexinvet.com/pro-kolin/p6230

Just an update, Jo.

We're on week 4 of 6 weeks at 5mg every third day for 31kg Shiva, an extra tapering step I've added on to the Lowrie protocol for the sake of the adrenals, given we've been on pred now for 10 months. Will do 2.5mg every third day next and then off completely.

Repeating blood tests next week which will be a month since the previous ones. The monocytosis is certainly explained by the pred so I'm not worried about that reading, but the elevated band neutrophils and the slightly elevated WBCs, and the C-reactive protein that's gone up but still within normal, are actually NOT explained by the pred, according to the link you shared, so really want to see those values normalise and not be part of a slide back towards any SRMA. All those values have been normal in some of our earlier blood test results, when pred dose was much higher. At the moment my best theory is that it's something to do with either the diarrhea he had (now resolved with first slippery elm and now psyllium husk which avoids the oxalates in slippery elm that are a kidney/bladder stone risk) or the pred-caused calcinosis, though I haven't seen any reference in any literature to calcinosis showing up in bloodwork, except for sometimes in elevated Calcium, which we don't have. We do however have elevated phosphates, which are the other component of the plaques formed in calcinosis.

I also thought you might be interested in this article. It was you who first warned me of Tri/Sulpha and you're the (godsent!) reason we managed to avoid using that antibiotic when the vet (who knows we're recovering from SRMA!) suggested it. The other antibiotic I'm aware of as being associated with causing meningitis in dogs is Metronidazole/Flagyl. But this article from human medicine also mentions others like Amoxicillin and NSAIDs. https://www.mdmag.com/journals/resident-and-staff/2005/2005-12/2005-12_02

Hope things are good your end.

Thanks again for everything.

Catherine I wanted to thank you for the warning about Metronidazole/Flagyl and to alert you, Jo, to the fact that several owners in the SRMA group on facebook I'm part of either gave Metronidazole before onset of SRMA or before onset of relapse. There is a warning about Metronidazole on the dailymed.nlm.nih.gov site under the listing for the drug that under the heading Central and Peripheral Nervous System Effects mentions aseptic meningitis alongside seizures and other possibly side effects.

What do you both think of tylan powder/tylosin as an alternative? (Other SRMA dogs have used this instead of Flagyl/Metronidazole.)

We have recurrent diarrhea. Originally opted not to give Metronidazole and instead resolved with probiotics.

But faecal culture at the time of the original diarrhea said:

Isolated anaerobic organism is likely Clostridium sp. Generally, Clostridium sp. is part of normal faecal flora. Gastrointestinal upset, stress
and protracted antimicrobial therapy can create an imbalance amongst the microbial populations.
Certain genera are normal gastrointestinal inhabitants capable of opportunistic infection (C. perfringens) and others are pathogens (C. difficle).
Amoxy/clav, Clindamycin and / or Metronidazole are recommended if antimicrobial therapy is necessary.

Now his bloodwork shows elevated WBCs and band neutrophils trending up. All was clear in blood test in May but then in June the bands were slightly up and now on August 1 the bands are much more elevated and the WBCs are also up. Since no other signs of infection, and tested clear for UTI, thinking it's probably the gut and if it's infected, need to treat. We've also had yellow specks and a HEAP of mucous in diarrhea for the past few weeks which I am thinking is pus/the white blood cells ie infection.

What do you think?

Since Metronidazole is off the table and every other infection we've had has been resistant to the other two drugs suggested, after we used them a lot in the early stages of the SRMA treatment... I'm thinking the tylosin. Love your advice and experience as to whether it's safe for SRMA dogs or if you've ever known it to cause problems?

Belated thanks for this Jo. You are the first person to tell us that elevated P is known to be associated with steroids. None of the vets could make sense of it. I don't suppose you can point me to a source on this so I can pass it on?

BTW we are now in week 6 of every third day dosing of 0.25mg/kg which for Shiva is 7.5mg every third day. Calcinosis lumps still a problem but we are treating with activated charcoal and hope it might help over time. Also now we have a new problem: elbow hygromas caused by the calcinosis on the elbows (love any advice you have on that) but otherwise doing well and now full of personality and better energy.

I think I'm deciding to add an extra 6 week taper after this one, of 5mg every third day. My logic for this is that as I understand it pred meets physiologic requirements not at one specific dosage for all dogs but within a range of 0.05-0.25mg/kg/per day. Our current every third day dose when divided by 3 comes out at 0.08mg/kg/per day. I figure since we've been on pred now for 9 months, Shiva's adrenals have been severely affected and need good support in coming back into function. So it seems like, given the range goes down to 0.05mg/kg/per day, it might be smart to stay on the pred until we get as close as possible to that lower end of the range? Going to 5mg every third day will equate to 0.05mg/kg/per day for us. What do you think? Do you think we ought do yet another taper after that too, ie go to 2.5mg every third day which would be 0.03mg/kg/per day so that it takes us BELOW the 0.05mg/kg/per day ie so that we know the adrenals are definitely having to kick back in, but we are keeping some prednisolone in the system during that period for support?

We don't want to stay on the pred any longer than necessary because we can't resolve the calcinosis until we're off the drug, but equally, no point getting off it only to have the adrenals not cope, and get a poor coping response to stress/excitement and then relapse and have to go back to the start.

Would dearly love to know whether you think this is sound logic based on your knowledge of how things work with the adrenals and what's happened for other dogs in your decades of paying attention to SRMA.. and how far down you'd take the taper before going off the pred.

Thanks as always,
Jane

Thank you so much for this Jo. I will have a good read and no doubt come back to you with more questions! The thing that worried me was that his WBCs were normal on all these fronts - normal band neutrophils, normal lymphocytes and no toxic change a month ago and now we're on lower pred so expected it should be normal still?

Reckon the band neutrophils and the toxic change could be caused by mouth infection?

Oh and yes I'm a big believer in the fish oil. He's been on that for some time now and I do believe it helps. The calcinosis as we've gotten to lower doses of pred is no longer appearing in new sites. I will be using activated charcoal on the lumps too, others have had great success with it drawing out the calcium/phosphate. He's been on a nutritionist-designed low-P diet recently too, to try to get down inexplicably elevated P in the bloods. It seems to now be coming down. Ever seen elevated phosphate in SRMA/prednisolone dog bloodwork before?

Oh and some good news: his CRP came back 0.7!!! It had been about 1 or 2 all during treatment but last month was 4 so I was worried it might be moving upwards... but I gather immunosuppressive doses of pred suppress CRP readings so you get an artificially low result while on those doses? So I was trying to tell myself it might have come up to the 4 just because it was no longer suppressed by the high doses of pred.. so DELIGHTED to see it be 0.7 now that we're on alternate day dosing of 0.25mg/kg and a week out from going to every third day dosing of 0.25mg/kg ie 7.5mg for Shiva at 31kg.

J

Thank you so much for this Jo, and Catherine.

I got some Metronidazole from the vet but am holding off on using it at the moment as we're now at last seeing some improvement just on the bland diet and the probiotics. I agree with you it's a good thing to have on hand and will resort to it if we need to.

The poop test came back showing clear of everything except for "moderate growth" of an anaerobe, most likely Clostridium. The pathology report said:

Isolated anaerobic organism is likely Clostridium sp. Generally, Clostridium sp. is part of normal faecal flora. Gastrointestinal upset, stress
and protracted antimicrobial therapy can create an imbalance amongst the microbial populations.
Certain genera are normal gastrointestinal inhabitants capable of opportunistic infection (C. perfringens) and others are pathogens (C. difficle).
Amoxy/clav, Clindamycin and / or Metronidazole are recommended if antimicrobial therapy is necessary.

So for the moment we're holding off on antibiotic but will resort to it if things go backwards.

We also did a blood test yesterday and though the liver enzymes are hugely better, the WBCs are concerning me because they are worse than the previous test a month prior, even though we are a month further along in terms of the pred taper (now on 0.25mg/kg ie 7.5mg every other day and a week away from transitioning to every third day dosing) and presumably we're a month further away from SRMA.

In the previous test all WBCs were normal except for a slight monocytosis and there was no toxic change at all.

However now, we have:

* mild toxic change
* slightly elevated Band neutrophils (0.4 compared to reference range of 0-0.2)
* slightly low lymphocytes (0.7 compared to reference range 0.9-4.1))

The monocytosis is slightly improved on last time (1.3 now down from 1.7 with a reference range of 0.2-1.0)

My question is:

Could the recent UTI (which we completed treatment for 11 days prior to blood test and tested clear of 4 days before the blood test) or the current diarrhea or a suspected current active infection of the pred-caused calcinosis on his tongue cause elevated band neutrophils and mild toxic change? And what about the low lymphocytes? (Because of course the worry is this bloodwork could indicate movement towards SRMA.)

Does your experience give you any insight into interpreting these results?

NOTE We're yet to attack the infected tongue calcinosis with antibiotics this time (though we have on several previous occasions) because we're waiting on a swab of the tongue to see if it can tell us anything about the strain of bacteria at play, and because we want to let his diarrhea subside before hitting him with any more antibiotics.

Warmest thanks
Jane

Jo, you always manage to comfort while providing straight information too. You're a big part of keeping me halfway sane.

We are into day 5 now of diarrhea. There was a sign of blood in the most recent poop, but hasn't been previously. Overnight the poor bugger woke me up to urgently go out four times - 1230, 1:15, 5am, 7:30 before breakfast. Normally we wouldn't go out between last walk at 10pm and after breakfast at 7:30am.

I took a foecal sample to the vet along with the urine retest yesterday. The good news is the UTI is clear. Nil WBCs and nil bacteria in urine! So the 3 day high dose enrofloxacin that was so rough on him was at least able to clear the E coli. Big relief.

The poop culture is still in process but the initial results showed negative for parasites (we haven't wormed him since January because of the fear these products are perhaps triggers for SRMA and he's an apartment dog in a big city so we're thinking chances of infection low but we need some natural worm prevention methods long term once we're through this.. I've heard things like pumpkin seeds?), and negative for giardia. The fecal occult blood was a weak positive but the vet says to ignore that? I have to ask her about it, but I'm thinking perhaps blood is to be expected with diarrhea? 

I see in my facebook group that other SRMA dogs have been prescribed Metronidazole/Flagyl for diarrhea and it's seemed to work? But Plumb's says it can have neurotoxic effects and it sounds pretty scary? We obviously don't want to go for what would be his 5th antibiotic in 7 months if it's not a bacterial infection, so I'm hoping the poop culture will tell us that?

My question is: what do you think of this drug Metronidazole/Flagyl for SRMA dogs?

What would you be doing for the diarrhea that's gone on this long?

He can be encouraged to play at times and other than the distress when he needs to dash out urgently, he doesn't seem at death's door. He is still eating and drinking. In fact, is hungry. But I don't want to let a stomach infection run and cause relapse. But I also don't want an antibiotic to cause relapse (others seem to think this has happened in their dogs?).

I'm sorry for being so high maintenance at the moment. Thank you again. Somehow it feels as desperate as ever that we can't seem to manage to get out from under these problems and have a clear run.

Jane & Shiva

The vets I've not found useful actually in helping to arrive at a decision about probiotics in the case of SRMA dogs. They seem to just say, Sure - go for it. But I'm not confident it's because they've thought it through for the specific case of SRMA dogs, but more because they just see probiotics as harmless in general.

I don't have advice that probiotics are to be avoided in SRMA dogs, or in cases of autoimmune disease generally. It's more just by extrapolating from what we do know, and in trying to think it through, that I arrive at the worry about whether they're a good idea or not, despite wanting to give them and knowing they will bestow benefits. I'm just worried about the possibility of other unintended other effects. Thinking it through: the treatment for SRMA has been to suppress an overactive immune system. So if anything we give an SRMA dog has an immunostimulatory effect, you would think there must be some risk of retriggering that process that caused the SRMA in the first place? Like, I've encountered advice in places like webmd that, for instance, some ingredient that is immunostimulatory should be avoided if you have an autoimmune disease. That's where I'm coming from with it. And from references to the fact that some probiotics are immunstimulatory, and some down regulate the immune system, but we don't seem to know which strain does which?

I think it does also explicitly say on webmd or somewhere similar that probiotics should be avoided in immunosuppressed individuals. That's where I'm getting that notion from. I think I've read reference to that being because they can cause infection in those people/animals? Which maybe isn't a worry for us when, as you say, we're no longer at immunosuppressive levels of pred. That's a good point. But there must be a hangover effect of immunosuppression after being on the high dose for so long? Ordinarily I wouldn't expect him to be getting UTIs but he has, and it's happened on our current low dose, so I'm thinking it's going to take some time for his system to get back to full strength?

Having said all that Shiva, 5 days after finishing the most recent antibiotic, came down with diarrhea that has lasted so far 4 days. Starting to see perhaps some improvement now. So I've bitten the bullet and decided that perhaps the benefits of probiotics outweigh the risks, and outweighs the risks of allowing his gut flora to stay out of whack, especially given the possibility autoimmune diseases could have some genesis in the gut. I've begun giving him a multi strain probiotic, hoping that by giving multistrains, any with immunostimulatory effects might be balanced by others with immunomodulatory effects.

What do you make of all that?

This process sure is exhausting.

Thank you again for being there, and for caring.

I absolutely think the same about the role of gut health in overall health. And I definitely think Shiva could benefit because he's been on 4 different types of antibiotics now in the past 7 months. The thing that has me worried though in the case of SRMA dogs is that it's said you shouldn't take probiotics if you have a compromised immune system?

Thanks Jo. In the end I went to use the Zesty Paws product but then changed my mind when I found on WebMD that one of the ingredients, the Organic Astragalus, is not advisable for those with autoimmune disease, I think because it's thought to stimulate the immune system, when what we're trying to do is damp down an overreactive immune system?

On that note, do you think probiotics are advisable or inadvisable for dogs recovering from SRMA? I can't tell with ether they're a good idea because they're immunomodulatory, or a bad idea because they're immunostimulatory? I know others have seen them make their dogs feel better, but I do worry about whether there could be also a relapse risk? But then you can find articles like this https://www.intechopen.com/books/probiotics-current-knowledge-and-future-prospects/probiotic-applications-in-autoimmune-diseases that seem to suggest mostly an immunomodulatory effect and a role in treating autoimmune conditions? What does your experience suggest about probiotics and SRMA?

J

Thanks so much Jo. What do you think about this one? Would any of the ingredients be dangerous for an SRMA dog?

https://au.iherb.com/pr/Zesty-Paws-Cranberry-Bladder-Bites-for-Dogs-Urinary-Kidney-Support-All-Ages-Chicken-Liver-Flavor-90-Soft-Chews/81147?gclid=Cj0KCQjwrdjnBRDXARIsAEcE5YngodGIa-IfPCigdig8lqSlREdnwyGcSXwdY1gqTSB0KHYp4M1nrKYaAmBbEALw_wcB&gclsrc=aw.ds

The ingredients are:

Cran-Max® Cranberry (Vaccinium macrocarpon), Concentrate (standardized for 7% [14 mg] proanthocyanidins), Organic Marshmallow Root, D-Mannose (naturally derived), Organic Astragalus, Organic Licorice, Nettle Seed, Pea Flour, Palm Fruit Oil, Garbanzo Flour, Tapioca Flour, Flaxseed Meal, Chicken Liver, Sunflower Lecithin, Coconut Glycerin, Powdered Cellulose, Rosemary Extract, Mixed Tocopherols, Sorbic Acid (Natural Preservative)

I'm asking because the below pasted comment is what our veterinary nutritionist said about cranberry supplements when I asked her. I'm not sure what to make of it because the reviews of products like the above one are so glowing online for preventing and even curing UTIs.

If you don't think this Cranberry Bladder Bites product has any contraindications for an SRMA dog and can at worst be ineffective, I'm inclined to give it a try.

Love your advice.

Thanks again,
Jane

Here's what she said:

I don't know of anything I'd recommend. If I were you, I would look for a product that's been given to dogs as part of a research study, preferably for a long period of time.

This product was used in the study below:

https://www.crananidin.com/
https://onlinelibrary.wiley.com/doi/pdf/10.1111/jvim.14613

There are probably a few others around too. Highly concentrated supplements containing anthocyanins make me a bit nervous; we did a safety study on a blackcurrant anthocyanin supplement at Massey and the lowest dose gave several of the dogs acute kidney injury, and the study had to be discontinued. The manufacturer of the supplement wouldn't allow publication of the results, but this may be the mechanism responsible for kidney injury due to grape and raisin feeding.

Having said that, lots of people seem to use it, despite fairly scanty evidence that it's effective, so hopefully it's safe!

Jo giving with food did help last night. He still got some nausea but not as bad as the first time and we both managed to get better sleep through the night. This morning, like last time, he's through the worst of it and quite happy and even a bit playful again. Didn't need to pee on the pee pad before we left the house for our little walk this morning so maybe the Enrofloxacin is starting to work on the UTI.

BTW in case it's useful for your massive repository of knowledge... Our veterinary nutritionist (in NZ) has said this about cranberry supplements for preventing future UTIs:

I don't know of anything I'd recommend. If I were you, I would look for a product that's been given to dogs as part of a research study, preferably for a long period of time. This product was used in the study below:
https://www.crananidin.com/
https://onlinelibrary.wiley.com/doi/pdf/10.1111/jvim.14613
There are probably a few others around too. Highly concentrated supplements containing anthocyanins make me a bit nervous; we did a safety study on a blackcurrant anthocyanin supplement at Massey and the lowest dose gave several of the dogs acute kidney injury, and the study had to be discontinued. The manufacturer of the supplement wouldn't allow publication of the results, but this may be the mechanism responsible for kidney injury due to grape and raisin feeding.
Having said that, lots of people seem to use it, despite fairly scanty evidence that it's effective, so hopefully it's safe!

So Jo, do you think products like these two (which I think are quite different from each other) are a better idea, although the bites still have cranberry? Or other things I can do to support urinary tract health? 

https://au.iherb.com/pr/zesty-paws-cranberry-bladder-bites-for-dogs-urinary-kidney-support-all-ages-chicken-liver-flavor-90-soft-chews/81147

http://www.naturalwonderpets-store.com/Primalix-NUMBER-1-p/pn1.htm

*****Would love if you could share a link to the kind of d-mannose product you'd recommend?

We have the third of the three-day course of doses tonight and I feel better about our ability to manage it now.

In terms of what happens then: do you know with UTIs whether you then stop treatment and wait before retesting urine to make sure it's clear or should you only come off once the urine tests clear? Vet is not experienced with SRMA at all, and has never done the short course high dose treatment for UTIs but is saying the lab says you stop the antibiotic and then wait a week and test urine... but doesn't that risk antibiotic resistance if you're coming off it before knowing the infection is gone? Or can't you get an accurate reading while still on the antibiotics? I'm not sure whether the concern would be you'd get a false negative because the antibiotics suppress the infection while still present even if it's not really gone? or a false positive because the infection can take some days after finishing treatment to clear? What do you recommend? *****Stop after the 3 days or only stop the drugs after doing a urine test and it coming back clear?

Thanks again, so much, for being there and for having the knowledge.

Jane & Shiva 

Jo, oh my god I can't thank you enough. You're an angel through all of this. I honestly honestly don't know where I'd be without you. I'm halfway round the twist with this 7 month odyssey as it is, but without you we'd be so much worse off. Thank you. I hope you know how much your presence means to us and I'm sure so many others you help.

I started him on the Enrofloxacin and hope to do a high dose short duration approach where we test the urine again after 3 days, based on the recommendations in Plumb's, which I bought a subscription with once you alerted me to its value a long time ago. It's a lifesaver.

I pored over the link you sent and it was so incredibly helpful, not least because of the mention of the added risk in intact male dogs (which Shiva is) of UTIs lodging in the prostate. The fact that Enrofloxacin is recommended for intact male dogs, as well as being the one the lab found Shiva's strains are susceptible to, makes me feel a little better for putting him through the "CNS stimulation" adverse side effect. The pills definitely make him feel nauseous but I gave it at midnight and by morning he was starting to feel somewhat less unwell. And it helps to know potentially with this approach maybe only 2 more days, maybe 3 if we have to wait for urine test results to hopefully show the infection has cleared before stopping. Thank you also for mentioning the seizure risk may well not apply to Shiva. Do you think the CNS stimuation is a potential relapse trigger for SRMA?

I also have ordered some cranberry-based, d-mannose bladder support to hopefully support the urinary tract and prevent any more UTIs. Do you think this is safe for an SRMA dog? https://au.iherb.com/pr/zesty-paws-cranberry-bladder-bites-for-dogs-urinary-kidney-support-all-ages-chicken-liver-flavor-90-soft-chews/81147

I really valued your pointing out the antibiotics to avoid for SRMA dogs. HUGELY appreciate that and will know to avoid them if they ever come up.

One thing I'm not sure of — would it be okay and not diminish the effectiveness at all of the Enrofloxacin to give it with food. I gave it last night on an empty stomach because I'd read that it was ideally given on an empty stomach? But like I say he definitely felt very sick, constantly licking lips, restless, lying-where he lies when he doesn't feel well (and have certainly felt in the past giving antibiotics with quite a bit of food helped him cope with them). Plumb's says this:

The presence of food in the stomach generally delays the rate but not the extent of absorption, but foods with increased divalent or trivalent cation concentrations (eg, milk) can reduce bioavailability.

But it also says it works this way:

Enrofloxacin is a bactericidal agent. The bactericidal activity of enrofloxacin is concentration dependent, with susceptible bacteria cell death occurring within 20 to 30 minutes of exposure.

... I'm not clear whether giving with food will diminish the "concentration" that's mentioned? What do you think? I think it would definitely be easier on him with food but need it to work properly so we can weather it on empty stomach if need be. And do you know if that mention of needing to avoid "divalent or trivalent cation concentrations like milk) means I can or cannot give it with his normal home-cooked dinner or, say, a can of Hill's k/d (which he's on at the moment as a low-Phosphorous diet to hopefully deal with high phosphate in his blood. (Not sure btw whether that is related to his calcinosis circumscripta from the pred that we're still battling, big lumps and still on his tongue too, but better there than it was and I think the lumps might be getting worse before they hopefully get better. )

Again, Jo, thank you from the bottom of my heart.
Jane & Shiva