VetInfo Digest     April 2001

This Month:

FIP Virus in Cats

Immune Mediated Thrombocytopenia (ITP)

New stuff and New Ways to Find Old Stuff

Kiltix (tm)

PPA

MoMetaMax (Rx)

Sevoflurane

It was probably inevitable, but the web site demands and the readership of the VetInfo Digest has finally reached a point where it is necessary for us to stop guaranteeing that we can answer questions within any specific time frame or even to guarantee an answer to every question.

I do not anticipate any time in the near future when it will be possible for us to return to the level of service that we provided in the first three years of vetinfo.com and VetInfo Digest. I am hopeful that the web site will satisfy most of the immediate need for information and that the newsletter will address enough current concerns to continue to be a very valuable resource. We do not intend to stop answering questions nor to stop making the best effort we are capable of to answer as many questions as possible as quickly as possible.

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Feline Corona Virus Infection and Feline Infectious Peritonitis

Feline infectious peritonitis (FIP) is caused by a virus in the feline coronavirus family. While this disease is of great importance because it is thought to be fatal nearly 100% of the time, it affects only a small number of cats. Another member of this family, feline enteric coronavirus (FECV) commonly affects cats, though. Some facts relating to FIP and FECV:

There are two recognized disease syndromes associated with FIP, a syndrome referred to as the "wet form" and a syndrome referred to as the "dry form". In both forms of the disease, once clinical signs start the disease is considered to be nearly 100% fatal.

The wet form of FIP is more easily recognized because affected cats have fluid accumulation in their abdomen which is usually very noticeable as the disease becomes advanced. Early signs of this form of the infection include fever, decreased appetite, decreased activity and weight loss. Some cats become icteric (jaundiced) as the disease becomes more severe so this disease must be considered in young cats that seem to have liver disease.

The dry form of FIP is a diagnostic challenge. In this syndrome the major internal problem is development of pyogranulometous (small focal infections) lesions scattered throughout the body. If the nervous system is the most affected organ system the signs tend to be neurologic. If the liver or kidneys are affected then clinical signs seem to indicate disease in these organs. Fever for no apparent reason is one of the major initial clinical signs of this form of FIP and there can also be weight loss, changes in vision, subtle neurologic signs or sudden onset of seizures in a cat who has not previously had seizure activity. As this form of FIP progresses it usually will eventually cause more severe neurologic signs and often causes recognizable eye disease, including visible inflammation in the anterior chamber of the eye (the portion in front of the iris that is easily visualized) and retinal hemorrhages and inflammation that are visible during an ophthalmologic examination. Due to the high variability in clinical signs this form of FIP is sometimes referred to as the "great pretender" of cat diseases -- it can mimic almost any other disease, making it necessary to consider FIP in the diagnosis of almost any severely ill cat.

General laboratory values for cats with FIP give some hints of the disease. The strongest hint that FIP may be present is a rise in serum protein levels above 8gm/dl. If fluid from the abdomen can be obtained for analysis it will usually have very high protein levels, as well. Mild anemia is often found in cats with feline infectious peritonitis and white blood cell counts may be low. The serum chemistry values other than protein tend to be normal unless there is significant damage to an organ from the disease. Since this does happen with some regularity, signs of pancreatitis, liver or kidney problems may be present. Dehydration associated with the fever, decreases in fluid intake and increased fluid loss occurs. It is sometimes severe enough to cause rises in the blood urea nitrogen (BUN) and creatinine levels in the blood, even when the kidneys appear to be functioning well based on other tests.

There are several available tests for feline corona virus. None of these tests can be considered to specific tests for FIP virus, though. The extreme similarity between FECV virus and FIP virus has been troubling to researchers involved in developing tests for some time. There is no difference between these viruses that is distinct enough to allow a test procedure to differentiate between them. For this reason, some people have always felt that these were the exact same virus behaving in two different manners. This group of researchers pursued the idea that if FECV virus was confined to the intestinal tract it caused transient diarrhea in kittens and had no effect at all on adult cats but if it somehow managed to make it into the body, including the circulatory system, it would cause the disease recognized as feline infectious peritonitis. The presumption was that the problem existed in the cat's immune system, with some cats possessing a weak defense against the FECV virus.

Other veterinarians have always felt that there must be two distinct viruses, an FECV virus that caused the minor problems and an FIP virus that was a killer virus. This theory was supported by clinical situations in which relatively large percentages of cats in a household develop feline infectious peritonitis in a short period of time. In one study, 17 of 39 cats in a household died of FIP within 6 months, making a contagious strain of FIP almost a certainty. (Panzero RA, 1992) In this case, the deaths all followed the introduction of one sick kitten to a cattery. The ability of some cats to transmit a virus capable of causing FIP made it difficult to see that this is not the most common way in which FIP develops.

The current theory for the development of FIP has come about by allowing for some aspects of both of the previous theories. In most cats, it appears that the cat is first infected with the FECV virus and that the infection persists for some time. Some cats constantly shed the virus for months or perhaps even years and other cats have intermittent shedding of the virus that seems to be due to reinfection during each cycle of shedding the virus. According to one study, 41% of cats in catteries are shedding FIP virus at any given time (Foley JE et al, 1997). With so many cats infected with FECV, the mechanism for development of feline infectious peritonitis is thought to be mutation of normal strains of FECV into viral strains that cause systemic disease and death. This mutation process may produce varying strength strains of virus capable of producing FIP and if these mutant viruses are shed in the stool or saliva, they are capable of causing FIP in the next victim, explaining the occasional outbreaks of contagious FIP infections.

Following the development of the mutant FECV virus causing FIP theory, it was felt that the differentiating factor between FECV infection and FIP infection could be the presence of a feline coronavirus outside of the digestive tract. If this was the case, testing body fluids and blood for the virus itself would be a definitive test for feline infectious peritonitis virus.

A relatively new test, the polymerase chain reaction or PCR test was developed which was sensitive enough to test cats for the virus itself rather than testing for an antibody response to the virus, like the original tests. There was a brief period in which veterinarians felt that the PCR test would be specific for FIP virus. Unfortunately, further research into this revealed that FECV virus was often found outside of the intestinal tract as it was carried there by white blood cells that had absorbed virus particle or through other means. (Herrewegh AA et al, 1995, Li X and Scott FW, 1994). There just hadn't been a test that was sensitive enough to the virus to pick up these small invasions into the body. The PCR test detects these coronavirus infections as easily as it does FIP infections. For this reason, testing was now back to square one, with no test that is currently available being able to provide a specific diagnosis of FIP. All we can detect is the presence of feline corona virus and it may be the relatively harmless FECV virus or it may be FIP.

There is some reason to go ahead and run feline coronavirus testing. In most cats, if the tests are negative it is best to look for other disease. During the end stages of FIP infection some cats do have negative antibody titers, though. This apparently happens because the immune system finally quits trying to produce antibodies in some patients. These patients are usually obviously ill, though. So a negative test in a cat that appears to be healthy is a good indication that FIP is not present. A positive test is not nearly as helpful, as it just indicates that the cat has been exposed to FECV and doesn't distinguish between this relatively benign disorder and FIP.

Feline infectious peritonitis infection is more common in kittens and young cats less than two years of age and in cats that are over thirteen years of age. This is probably due to the relatively weak state of the immune system in young cats and geriatric cats. It can occur at any age, though.

At the present time, clinically apparent FIP infections are considered to be nearly 100% fatal. There are anecdotal reports of FIP "cures" but most of the time the cats that are reported to be cured were never really proven to have FIP with a high degree of certainty. There are a few cases in which the disease was well documented and a patient survived, though. The use of prednisone or other corticosteroids to suppress the immune system can prolong the course of the disease, for as long as several months, but does not appear to be able to suppress the reaction to the FIP virus long enough to allow cats to live through the infection, except in rare cases. It may be beneficial to use interferon in addition to corticosteroids. In most cats, from the time that FIP becomes the most likely suspect until the time that death occurs is one to three months.

Most cats that develop FIP live with at least one other cat and it is more common for affected cats to be from households with more cats than this. For this reason, the most common question that we get about FIP is how to protect the other cats in the household from infection. There is a vaccine for FIP and it does appear to work to prevent the infection in cats who have never been exposed to FIP OR FECV. However, it does not provide any additional protection for a cat that already has the FECV virus so post-exposure vaccination is not likely to be helpful. The best use of the vaccination is to try to prevent infection with FECV in a cat who has not had previous exposure and is being brought into a household in which exposure is likely, or for attempting to eliminate FIP in a multiple cat household by isolating kittens from all other cats after early weaning, until they can be vaccinated twice with the FIP vaccine. Once the household is FIP free, all cats added to the household should be FECV free and should be quarantined for at least a month to three months prior to mixing with the other cats, in order to maintain an FECV free environment.

In a household with a low number of cats, there is not a significant increase in the risk for FIP after a cat in the household has it. This may seem like it makes no sense, at first, but the apparent need for the FECV virus to mutate into an infectious form, in most cases, even if a cat is infected, explains why the risk is not great for FIP outbreaks. In a study of 820 cats from households in which FECV exposure had occurred, there was no statistical difference in the rate of development of FIP from households in which FIP had recently been diagnosed and households in which FIP had never been diagnosed but FECV was present (Addie, et al, American Journal of Veterinary Research, April 1995). There have been a few cases in which multiple cats in a single household developed FIP within a short period of time, apparently because of direct transmission of an infectious form of FIP virus itself, but these outbreaks are rare. In the twenty-two years that I have been in practice I can only remember one incidence in which we had an outbreak that resulted in multiple FIP deaths in a group of cats at one time. This was a situation in which a client was feeding a large number of "outdoor" cats and approximately ten of them died within a month or so. Other than this outbreak, our experience has been that the risk to other cats in the household is not much greater for development of FIP if they are exposed to an infected cat, or not.

Feline infectious peritonitis is a frightening disease for cat owners because it is fatal so often. It is tentatively diagnosed (included on "rule out" lists) many more times than it is actually present, because it is hard to rule out and because it can mimic a great number of other conditions. When FIP is being considered as a possible diagnosis it is important to remember that there is not an accurate test for it, other than biopsy of affected tissue or post-mortem examination. It can be diagnosed with near certainty in some cases, due to the presence of clinical signs and supportive lab work but not with absolute certainty without having affected tissue samples. Once a cat in the household has FIP, it is reasonable to assume that all the cats have been exposed to feline coronavirus but it is also true that the risk to these cats of developing FIP is not significantly greater than the risk of any other cat who has been exposed to feline corona virus. With just a little luck, a cat with FIP in a household with a small number of cats will be the only case, especially if no new cats are added to the household.

 

Immune mediated thrombocytopenia

I spent some time researching immune mediated thrombocytopenia this month because my own rottweiler, Tess, developed this disorder. Her case probably involved a reaction to medication dispensed by her veterinarian. In her case, the medication that seemed to induce this condition was cephalexin, an antibiotic. Although cases of ITP have been reported in conjunction with the use of cephalexin, this was the first case that we had seen from its use.

Immune mediated thrombocytopenia (ITP) can be translated as a disease causing decreased platelet numbers that is due to a problem with the immune system. Thrombocytes, or platelets, are necessary for blood clotting to occur, so this disease causes a bleeding disorder. Platelets are formed by the bone marrow by cells referred to as megakaryocytes. These cells fragment to produce platelets, with up to 200 platelets being formed from one megakarocyte. The cell wall of the platelet contains active receptors and chemicals which aid in the clotting process, allowing platelets to adhere to one another to react to blood clotting needs. Normally, platelets have about a ten day lifespan in the blood stream. Their activity can be inhibited by a number of medications, the most common of which are aspirin and other non-steroid anti-inflammatory medications. When platelets are old they are removed from the blood stream by the spleen, primarily.

ITP can be a primary (or idiopathic) disease, in which no apparent cause for the condition can be identified. It can also be a disease that occurs secondary to other immune stimulation, such as blood parasites, viral illness, metastatic cancer or drug reactions. If ITP and immune mediated hemolytic anemia (IMHA) occur at the same time, there may be a common underlying cause or one of the diseases may be primary but inducing the other one. This combination of ITP and IMHA is referred to as Evan's syndrome and occurs in about 5% of the cases of IMHA.

ITP typically occurs in middle-aged dogs and female dogs are a little more likely to be affected than males. There doesn't seem to a strong breed predilection, but cocker spaniels, poodles and Old English sheepdogs may be predisposed to this condition. (Compendium on Continuing Education, March 1995).

Platelet numbers usually run between 200,000 platelets/ul and 500,000 platelets/ul, but spontaneous bleeding appears to be unlikely if the platelet level is above 50,000 to 75,000 platelets/ul. Some dogs have consistently low platelet numbers, in the 100,000 to 150,000 range, without ever experiencing a problem. This may be a from poor platelet production or may be a chronic case of immune mediated thrombocytopenia in which the bone marrow is able to compensate for the destruction of platelets that the dog is experiencing.

When hemorrhage occurs due to a platelet disorder, it is more common for the small capillaries to be affected, leading to subcutaneous bruising, than for spontaneous hemorrhaging to occur. In some cases, though, nosebleeds or black colored stools from gastrointestinal bleeding are the first signs of a problem. The subcutaneous hemorrhages, referred to as petechiae if the bleeding consists of very small bruises and ecchymoses if there are larger more typical "bruises", are more easily seen in the oral cavity, around the eyes, around the vulva or penis and other areas in which pink tissue is easily seen. For examples of this, from my dog's case, follow this link: www.vetinfo.com/subscriber/photos

When poor platelet function is discovered, either through lab work or through clinical signs, it is important to be as certain as possible that the problem is destruction of platelets and not poor production of them or deficient function caused by diseases such as von Willebrand's disease or by medications such as aspirin or non-steroidal anti-inflammatory medications. It can be very helpful to examine a bone marrow aspirate to be certain that there is not a problem with platelet production. A thorough medication history should be asked for by the veterinarian and provided by the client.

Once it is established that ITP is likely, it is important to look for potential underlying causes of the condition. In our practice, the most common non-spontaneous cause of ITP has been drug reactions. The most common culprit has been sulfa-trimethoprim combination antibiotics. This was particularly true when we used these medications long term for skin disease (longer than 15 to 20 days), which we no longer do. We have seen ITP that appeared to be related to other medications. Modified live virus vaccinations will often cause a temporary decrease in platelet numbers and can lead to full blown ITP in rare instances. Spleen or liver disorders can lead to increased platelet destruction. Blood parasites (esp. Ehrlichia platys and Babesia organisms) and viral or bacterial infections (esp. leptospirosis) may also lead to increased platelet destruction. Cancer, especially hemangiosarcoma and lymphoma, is also a fairly common cause of secondary immune mediated thrombocytopenia.

The following medications have been implicated as potential causes of ITP: antibiotics (sulfas, sulfa-trimethoprim combinations (Bactrim, Ditrim, Tribrissen, Rx), penicillin, cephalexin (Keflex Rx), metronidazole (Flagyl Rx), chloramphenicol); phenothiazines, phenobarbital, azathioprine (Imuran Rx), chemotherapeutic agents, levamisole (Levasole Rx), methimazole (Tapazole Rx), propylthiouracil, non-steroidal anti-infammatory medications (aspirin, phenylbutazone, etc.) and cimetidine (Tagamet Rx).

Lab work is important in the diagnosis of immune mediated thrombocytopenia. It is important when evaluating platelet numbers to recognize that some breeds seem to have consistently low platelet numbers, especially Cavalier King Charles Spaniels and greyhounds. If there is a moderate decrease in platelets (50,000 to 75,000 platelets/ul) but spontaneous hemorrhage, it is usually best to look for a primary cause, such as ehrlichiosis or cancer. If there is severe thrombocytopenia (very low platelet numbers, especially < 25,000 platelets/ul ) then primary ITP or a drug reaction are more likely.

Lab tests other than platelet counts can be helpful, too. Bone marrow evaluation can be useful and is definitely indicated if there is also anemia that appears to be non-regenerative (no new blood cells to replace the missing ones). Tests for tick borne diseases in both dogs and cats, feline leukemia virus, feline immunodeficiency virus, immune-mediated hemolytic anemia (auto-agglutination, Coomb's test) and other bleeding disorders may all help to pinpoint a diagnosis.

Treatment for ITP involves removing the primary cause, if possible, and then using corticosteroids to suppress immune system destruction and usually using doxycyline (an antibiotic) if there is any chance of a tick borne disease since testing for these usually takes several days to weeks. In critical cases intravenous use of dexamethasone, a corticosteroid, may be called for, but in most cases it is possible to use prednisone orally. In really severe cases of ITP, in which spontaneous hemorrhage has occurred or seems very likely to occur, it may help to use transfusions of fresh whole blood, platelet rich plasma or cyroprecipitate. Transfusion sometimes incites the immune system even more, so transfusion should be given only when it really seems to be a necessity.

Cyclophosphamide can be given to stimulate platelet production in severe cases of ITP. This is usually a one-time treatment. Azathioprine (Imuran Rx) can help as a supplement to prednisone in some cases. Danazol has been reported to be helpful by some researchers but has not been consistently useful in all clinical trials. In cats, chlorambucil given every two weeks appears to be effective as a treatment for ITP. For very resistant cases of ITP it may help to remove the spleen, as it is the major site of platelet destruction in the body.

If there is not an underlying cause that is extremely serious in its own right, such as hemangiosarcoma or lymphoma, the prognosis for dogs with ITP is generally good. Cats do not get this disease as often and do seem to be a little harder to treat but their prognosis is at least fair. In drug reactions it may be necessary to treat for as short a time as two to three weeks after drug withdrawal. In primary ITP treatment may be necessary for life in some dogs and cats but often can be discontinued after two to three months. Periodic monitoring of platelet levels for several months after apparent recovery from immune mediated thrombocytopenia is a prudent course of action.

 

New Products, Promotions and How to Get Old Standbys

Kiltix (tm) is not a new product, but it is available free from your veterinarian if your dog is on Advantage (tm). This is a tick control product that is safe to use in conjunction with Advantage, for dogs only. If your favorite flea control product is Advantage but you occasionally need a tick control product, ask your vet about Kiltix. It is not available for cats.

Many of my clients and subscribers to VetInfo have been searching for a source of phenylpropanolamine (PPA) since it was banned for human use by the FDA. There is a phenylpropanolamine product approved for dogs and the FDA has not applied the ban to this product at this time. The brand name for this medication is Proin. I believe that your veterinarian would need to obtain the product for you, but the phone number for the company is 1-800-874-9764, in case there is difficulty finding a source. Proin is available in 25mg/ml drops, as well as 50mg and 75mg tablets. Phenylpropanolamine is also available from Wedgewood Pharmacy, a mail order compounding pharmacy in New Jersey. The phone number for Wedgewood Pharmacy is 800-331-8272.

MoMetaMax (Rx) is another new product for treating infected and inflamed ears. It contains an antibiotic and antifungal ingredient along with a new corticosteroid, mometasone furoate (same ingredient as Nasonex Rx), which Schering-Plough, the manufacturer, promotes as having a faster anti-inflammatory effect than currently available corticosteroids. Ear inflammation is a frustrating condition to treat in dogs, so having additional choices in medications should be beneficial for some pets.

Sevoflurane (Sevo-Flo Rx) is an anesthetic which was approved for use for pets in 1999 but is beginning to have broader acceptance at this time. It is considered to be slightly superior to isoflurane as an anesthetic agent due to slightly quicker recoveries and less irritation of the airways. Due to the costs involved in changing anesthetic vaporizers, new anesthetic gases take some time to catch on with general practitioners. I think that isoflurane has a very good track record and do not feel pressured to make a change due to this. I find that my clients are just now starting to catch on to the benefits of isoflurane over other anesthetic gases and some have been asking if we use isoflurane. If you ask your vet this question and he or she says, "No, but we use sevoflurane," that would be a good thing, not something to worry about.

Thanks for Your Support!

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