Truly baffling critical illness, presenting identically in two 21 week old kittens.

Hello,

To preface this, I have already seen several veterinarians, and I know that I need to see an internal medicine specialist at this point. However, since everyone seems baffled, I wanted to reach out online and see if anyone has thoughts. 

I have two 21 week old pure bred ragdoll kittens. They've been critically ill for 3 going on 4 weeks now, and nearly died on a daily basis for about 9 days of that. They've never been outside or exposed to other animals. I got them from a very ethical and quality breeder with well cared for cats clear of all disease by evidence of laboratory testing at UC Davis who has never had a kitten develop FeLV, FIV, or FIP. We were in New York City, and during the recent feline avian flu outbreak, but their symptoms don't really match that. We are now in Colorado. 

This all began with a little bit of a respiratory illness and slight eye glaze/goopy, but they no longer have those symptoms they began with. Their primary (and most life-threatening) symptom is high fever (105-107), which seems to be controlled by relatively low-dose prednisone (5mg x2/day) but returns when we try to taper them off of it. They've had 3 antibiotics (Clavamox for 14 days which they just finished today, Convenia 1 14-day injection 2 weeks ago, Baytril x3 days 2 weeks ago). They have been on highest quality food (Weruva Luxe, The Honest Kitchen) plus vet-prescribed multivitamin, b-complex, omegas, and probiotics. They've had around-the-clock care the entire duration of this, and I've been set up for most of it to be able to deliver fluids at home for them when needed. After receiving the Baytril (the only thing I can think that precipitated this), they lost their ability to walk over about a day and then became completely unresponsive until I took them to a new vet who began the prednisone and Clavamox. 

They slowly regained their ability to walk over about two weeks, and began playing. Honestly, when on steroids they seem mostly normal and seem very happy. Even when they were critically ill, they still tried to eat a little bit and they groomed themselves. They obviously want to live but these fevers are just awful. Obviously I'm writing this as one of them has again deteriorated into high fevers and bad symptoms after tapering the prednisone. I know this all makes anyone scratch their head and reach for the FIP diagnosis. I also know they don't meet most of the criteria for that based on common diagnostic patterns by several experts. They also got about 95% better on prednisone and antibiotics and 48 hours ago were acting normal and playful...my understanding is that FIP doesn't wax and wane that significantly... cats tend to just get sick and stay sick. They also do not have even a positive RealPCR to the corona virus at all, which was done at IDEXX and is very reliable. I realize it can be negative... but even my current vet doesn't think it's FIP, he and his hospital team are just baffled by the fevers as we cannot figure this out. 

Here are the tests and results that we've ran (same for both cats): 

FeLV by RealPCR    NEGATIVE    

CYTAUXZOON FELIS by RealPCR    NEGATIVE    

BARTONELLA PCR    NEGATIVE    

ANAPLASMA SPP by RealPCR    NEGATIVE    

EHRLICHIA SPP by RealPCR    NEGATIVE    

FIV by RealPCR    NEGATIVE    

FELINE CORONA VIRUS    NEGATIVE    

CRYPTOCOCCUS SPP    NEGATIVE    

CALICIVIRUS PCR    NEGATIVE    

TOXOPLASMA GONDII    NEGATIVE 1

Stool - Negative for any parasites or infection
Lung x-rays - clear
Abdominal ultrasound - clear of signs of fluid
Eye tests - completely normal
Mouth/Ears - completely normal
Nose - were sneezy for weeks before all this but now clear of this for weeks
Eyes - had slight watery and goopy eyes earlier on, but has been cleared for weeks

Blood work (this is one cat, but they are similar): 

WBC was slightly elevated (18.0)
RBC was slightly low (7.70)
HGB was slightly low (9.7)
HCT was slightly low (28.0)
MCV was slightly low (36.0)
Neutrophil = 83.2
ALP - 12
ALT slightly low at 25
Albumin slightly low at 2.5
Total protein - 6.8
Globulin - 4.3
ALB/GLOB ratio - 0.6
Bilirubin - 0.1
BUN slightly low at 12
BUN/Creatine ratio - 20.0
SDMA - 8
Hemolysis Index - Neg
Lipemia Index - Neg
Reticulocyte - slightly low at 8

ANY ideas at all? This is exhausting and heartbreaking. Thanks. 

I really have no idea and I have never heard of something like this.  If the steroid is helping it could well be something that is autoimmune in nature.  It can't be FIP because they are negative for the corona virus.  FIP is a mutation of the corona virus so no corona virus means no FIP.  There are some vet techs here as well as people who have been involved in rescue for quite some time, maybe they have seen something like this.

The chemistry profile and CBC don't look indicative for FIP to me, but I see that the following aren't on your list and wonder if the vet has taken these into account:

Calicivirus (the virulent form)
Bartonella henselae
Mycoplasma haemofelis aka Hemobartonella
Tularemia, Yersinia, Salmonella, Clostridium
Systemic lupus erythematosus
Heartworm
Pyelonephritis

Congenital (i.e., poorly developed vital organs, heart, etc)

My concern would be Mycoplasma above all, the virulent form of Calicivirus, or Pyelonephritis to have ruled out immediately.

Ask your vet about blood cultures, and urine culture and sensitivity testing (the latter to rule out Pyelonephritis or nasty bacteria often found in the urine).

Ask vet his opinion on using doxycycline, or if it would be contraindicated with the unrelenting fever.  That they respond using steroids indicates a significant inflammatory condition going on and the high unrelenting fevers could be in response to fighting that or staving off a significant bacterial or viral load. 

Internal medicine specialist or Immunologist opinion ASAP (and if your vet has access to VIN, he can also access other vets and specialists there for additional guidance)

Tomorrow's Monday, please ask your vet to be consulting specialsts for additional guidance - with every fever spike, there could be underlying damage occurring, so a specialist could have other ideas to test for or treatment approach.

I am a human doctor, a retired specialist in internal medicine, not a vet. The response to steroids suggests an autoimmune disease such as lupus erythematosis, although the fact that the illness, whatever it is, has occurred in two siblings at the same time, is most unusual.   If the steroids had been given when there was an acute bacterial infection, the illness would have become much worse, akin to blowing oxygen onto a fire! This is a reason why steroids should never be given when there is a risk that there is an infection present. I recall a lady who had been given steroids when she was suffering an acute streptococcal infection and she developed osteomyelitis (infection of the bone) of both knees. The steroids were ceased immediately but, for the rest of her life, she was confined to a wheelchair. 

I agree with @cat-tech that the kittens should have blood cultures taken but, I must apologise to him as I cannot agree that there is much evidence for the list of infectious diseases that he has given. Although a micro-urine has not been taken, and it must be, the presentation is also unlike that of an urinary tract infection such as pyelo-nephritis.  If there had been any acute infection, along the lines that @cat-tech had suggested, then there would usually have been further evidence for this, such as clinical (this word means "bedside") evidence, on examination. The steroids would not have just suppressed the illness, but would have aggravated it, as I have already described. 

In fact, I agree that the whole presentation is unusual and I believe that the diagnosis will not be made until the tests are repeated with anti-nuclear factors, micro-urine and blood cultures added and we see what will develop. 

I must stress that my experience is with internal medicine in humans -  cats may react differently to similar illnesses so that any advice that I give should be checked with a veterinarian. 

I also do understand how distressed @GracedeEtoiles  must feel and all my sympathy goes out to her.

With all best wishes,

Geoffrey

Thank you all for your thoughts and support. We're in a life and death battle to figure it out, and losing at the moment. 

Oh GracedeEtoiles, I so hope and pray for a miracle for your two precious babies!