Prolonged Fever with No Diagnosis of Cause

My dog came down with signs of fever and lethargy about a week ago. We took her to the vet and went through the suggested series of tests to diagnose the underlying cause, but all of her tests have come back negative. I'm desperate to figure out what is making her sick!

A little recent history: She had a tick on her neck late this past summer, but the tick itself was tested for Lyme and came back negative. About 4-5 weeks ago we noticed that she was licking her wrists quite a bit, (a habit she'd had on and off) and then a small elevated nodule appeared on the inside of her wrist. We were told it was likely a granuloma from too much licking and we treated it with Cortisporin cream and it disappeared after about a week.

We've done all of the tests listed above, plus our dog has been on several antibiotics over the course of our investigations in an attempt to treat the most likely infections that might cause the symptoms, but her fever has still not lowered significantly from its average 40 degrees celsius. Metacam has been used to try to reduce her fever but has not worked, so she's been taken off of it. I can't remember the names of the specific antibiotics now, but Clavaseptin was one she's been on I think and Doxycycline another and they gave her another one about 4 days ago to target Leptospirosis, but it's been somewhat ruled out at this point. Today my vet said she's going to put her on the best possible range of antibiotics to attack the widest range of possible issues, but the names of the antibiotics escapes me for the moment. We've sent off blood samples for Leptospirosis and Bartonella...Have not received the results yet.

We're running out of tests to do (not to mention money) and we're just about at our wits end. If anyone has any suggestions based on past experience as to what this might be, I'd really appreciate your input.

Julie

[Arnold L Goldman, D.V.M.]

Dear Housefly,

When a fever unassociated with an obvious and known condition is evaluated fully and no underlying cause is determined to that point, the condition is termed "fever-of-unknown-origin (FUO) ." That description implies that a through workup has occurred and acts as a reminder that the vagaries and nuance of the operations of "biological systems" remain incompletely understood. Physicians and veterinarians can only pursue known possible diagnoses in an effort to rule them out and hopefully be left with one diagnosis that fits the signs, can be proved by test and treated by medicine or surgery. I don't doubt that ther are many diagnoses yet to be characterized that we see and call something else, or nothing if they resolve spontaneously. "Fever-of-unknown-origin is likely a catch all term for several such diagnoses in many species. Thorough testing helps us avoid calling a pet's situation by that name, because when we do we are left with empiric medication trials (antibiotics, steroids) in the hope of picking correctly. While carefully chosen, such attempts are no more than scientific guesses. Obviously not an ideal situation.

Your doctor has done a thorough work up. I assume that in addition to a negative Lyme disease test, that a more comprehensive "tick serology" profile was run. Such a profile, in addition to Lyme disease also includes Rocky Mountain Spotted Fever (RMSF), Ehrlichiosis (Anaplasma) and possibly Babesia as well.

RMSF in particular can cause FUO as well as polyarthritis. You did mention licking and there was a reason to aspirate all those joints. Serology can rule out RMSF.

At this point there are so many variables, response to therapies may well be the key to the problem. If you are dissatisfied with the lack of progress made, perhaps see a baord certified internal medicine specialist (credential: DACVIM)  or at least have them review what has been done.

Good luck and please let us now how things turn out.

Best regards,

Arnold L. Goldman DVM, MS
MedHelp & PDOC

[Housefly]

Just to make a quick correction, I believe what the vet found in the knee joint tap were neutrophils. I'm getting my terms all mixed up.

[Housefly]

Thank you for your response.
I will mention the tick serology profile when I talk to my vet today. I live in Montreal, Canada, so I don't know how prevalent RMSF is around here, but it certainly wouldn't hurt to do a thorough blood examination for any possibilities if they haven't already done that.

The way my vet suggested we proceed is to wait until Thursday to see if the last antibiotic will have an effect and if it doesn't then we will put her on Prednisone.

But from what I've read it seems that there are risks involved if we give her Prednisone and she is fighting a virus, is that correct?

Thanks again!

[Arnold L Goldman, D.V.M.]

Well, sometimes a viral infection itself is the issue and sometimes the immune reaction to the presence or former presence of  viral protein is. There is also a difference between anti-inflammatory and immunosuppressive doses of corticosteroids, of which prednisone is one example. Polyarthritis may be immune mediated, may be associated with fever and may be treated with corticosteroids in the absence of a proven viral or previous viral infection. It is the "immune complexes", basically antigen-antibody complexes that are themselves inflammatory in joints and in small vascular beds, such as the kidneys for example. Your doctor is best situated to parse all this for you, having direct knowledge of the case. To me, it sounds like you are in good hands.

Please let us now how it turns out.

Sincerely,

Dr G

[Housefly]

It's been a while, but I'd like to add an update to let you know what's happened. (I hate when people don't post updates!)

My dog has been on Prednisone for several weeks now and the fever disappeared almost immediately as expected. She's finished all courses of antibiotics (5 in total I think) and we are slowly reducing the Prednisone dosage with each vet visit (every 3 weeks or so). She's gained back the weight she lost and then some. Is eating very well and is her old self again.
Her CBC was back to normal at last check, so things are looking good.

They still are not exactly sure what caused the fever as all tests for viral infections came back negative, but the general feeling is that Leptospirosis (which they found a tiny hint of) or something of the sort put her immune system into overdrive.

Thanks again for your input. The vets we've been dealing with have been excellent, but it's always nice to get another opinion.