VetInfo Digest March 1998
This issue
Hard to Understand problems and illness
Heartworm Disease:
Immune Mediated Hemolytic Anemia
Feline Leukemia Virus Infection
New stuff
Heavy Metal Dermatitis
Hard to Understand
There are several groups of illnesses and problems in pets that seem to generate the most anger in clients towards themselves and their veterinarians. I think the common bond between these problems is the complexity of these diseases and the desire of most people to find a simple cause and effect relationship in medical disorders. It is very difficult to understand some diseases. So difficult that many veterinarians do not have a firm grasp of them and therefore have little chance of successfully explaining them to a concerned pet owner. In other cases, no one understands the disease process, or at least no one has published a scientifically valid explanation for how or why a disease or disorder occurs. We expect our health care professionals to understand what is happening to us and our pets, to be able to provide a rational method for avoiding health problems or to at least be able to treat them when they do occur. It's an impossible expectation, but that doesn't stop us from having it.
Heartworm Disease:
In my office, I get more reaction to the diagnosis of heartworm disease than any other illness in dogs (and occasionally cats). There is always a moment when the client is sure that we did not inform them of the risk of heartworm disease. Particularly when it occurs in a cat, because many clients are right in that instance. Prior to the availability of heartworm prevention for cats we simply didn't discuss it much because there wasn't much we could do about it. Inevitably, we have missed some people in going back and trying to make up for that. Another problem with heartworm disease is the mode of transmission and the variability in life span of affected dogs. It sounds like science fiction.
A mosquito bites an infected dog and picks up a microscopic baby heartworm (a microfilaria) from its bloodstream. This baby can never grow into an adult unless it makes the trip through the mosquito. Why not? The major reason is survival. Parasites depend on their hosts to live long enough to transmit them. Dogs often have 60,000 or more microfilaria in their blood stream. Suppose they could all grow up into the typical adult heartworm, which is a few millimeters thick but 15 to 20 cm in length. The dog would clearly die quickly. So the heartworm has developed babies that must pass through a mosquito. Once activated by the mosquito they can grow. Obviously, the mosquito has a big problem now, too. If the larvae grew up in it, the mosquito wouldn't last long, either. Fortunately for the mosquito there is a next blood meal and it transfers the pesky parasite to a new host. The baby heartworm is now called an infective larvae. It spends about 5 months finding its way to the dog's heart and pulmonary arteries and growing into an adult. This is the second confusing thing to explain to pet owners. We can not test for heartworms from the time of the mosquito bite to the time it grows into an adult. If we test during these five months the test will be negative. A year later it will be positive, usually after a year of heartworm prevention medications have been administered. Pet owners often find this difficult to believe. Even worse, the test only detects female heartworms so some dogs show signs of heartworm disease eventually, despite years of negative tests using pretty accurate test kits. They just have all male heartworm infections.
The last difficulty in explaining heartworms is the extreme variability in the disease process. We have done an autopsy on an eight month old puppy that we are pretty certain died of heartworm disease since it had about 50 heartworms already present in its heart and pulmonary arteries. We have diagnosed heartworms in a dog at two years of age, had its owner refuse treatment and then seen it live to twelve years of age prior to developing heart failure, which may or may not have been from heartworms. The reason for this discrepancy is based on the number of heartworm present and the dog's individual immune response to those worms. Heartworms do not directly damage the heart or pulmonary arteries. They live in areas of turbulent circulation and this causes some damage to circulating red blood cells. The damage leads the red blood cells to clump in mini-clots. These little clots are very abrasive. They irritate the lining of the blood vessels in the lungs, making them thicken and become less elastic. Eventually this leads to enough occlusion to cause the blood pressure in these arteries to exceed the blood pressure the heart can pump against. Chronic heart failure develops. A lot of worms cause a lot of damage in a hurry. A small number of worms produce damage more slowly but it still occurs over time. A few dogs probably have minor blood clotting disorders which are beneficial to them or other immune deficiencies reducing the reaction to the parasite. All of these factors contribute to an extreme variability in the length of time a dog may live with heartworms and the severity of the disease that affects them.
Heartworm treatment kills a small number of dogs who have severe reactions to the death of the worms or that react to the medication used to kill the worms. With the newer treatment available now the death rate is probably around 2 to 3%. Probably 80% or more of dogs that are not treated eventually die of heartworms. Yet many owners can not bring themselves to make the decision to trade a 2% risk that their pet may die in the next few weeks for a 78% ( .98 treatment survival rate x 0.8 percent natural death rate) chance that they can prevent future premature death of their pet. The fear appears to be in making the decision. Clients are upset when they choose to treat and their pet dies and when they choose not to treat and come in months or years later with a pet who is now so severely affected that treatment is highly risky or even impossible.
At least we don't have to explain heartworm prevention in an area in which heartworm disease rarely occurs. For me, this has to be a tough problem. It would be even harder to explain the results of a positive heartworm test in these areas, since the test has about a 1% false positive rate. If the likelihood of actual infection is only 1 in 1000, then there are 9 false positives for every truly infected pet. Lots of additional evidence may be necessary to justify treatment in these localities. Even in our area we usually try to confirm the diagnosis with additional testing unless the pet has obvious clinical signs suggestive of heartworm disease.
Heartworms are a preventable illness in both dog and cats. If you live in an area in which heartworms are endemic, make the easy decision and start them on prevention early and keep them on it lifelong.
Immune Mediated Hemolytic Anemia
On line, immune mediated hemolytic anemia (IMHA) is probably the disorder that is asked about most commonly. It is also known as auto-immune hemolytic anemia (AIHA). It is sometimes confused with immune mediated thrombocytopenia (ITP) which is a different problem that is usually more responsive to therapy.
IMHA is an insidious disease and it can be very frustrating for pet owners and veterinarians alike. It can have an extremely rapid onset, with some cases reported to proceed from an apparently well dog to death in twenty four hours. This is not the ordinary course of the disease but it is frustrating when it occurs. Many dogs do recover from IMHA but it is often fatal even with proper and aggressive treatment.
Somewhere between 40 and 60% of the cases of IMHA are "primary", meaning that they can not be linked to a cause. This means that between 40 and 60% of the cases of IMHA are the result of another illness that eventually leads to immune mediated hemolytic anemia. Recognized primary causes include cancer (most common), drug reactions, vaccine reactions, systemic immune system disease and infectious illnesses such as feline leukemia virus, ehrlichiosis and heartworms.
IMHA occurs when an antigen (foreign substance such as a virus, bacteria, protein, etc.) sticks to the red blood cells and the body's immune system attacks. Unfortunately, the immune system is not smart enough to attack the antigen only. Red blood cells are damaged in the attack and either break up in the circulation (intravascular hemolysis) or are removed by the body's normal mechanisms for getting rid of defective blood cells in the spleen and liver (extravascular hemolysis). In either case the result is anemia, which can develop slowly or very rapidly.
Pets with immune mediated hemolytic anemia may be weak, depressed and unwilling to eat. They will develop pale mucous membranes (the normally pink ones in the mouth and around the eyes). Later they will become jaundiced, often have enlarged lymph nodes, may develop heart murmurs, fevers or darkly discolored urine. Visible bleeding doesn't normally occur but is possible.
Diagnosis is made on the appearance of red blood cells on a smear, the presence of anemia, especially if it is regenerative (immature red blood cells are present in the blood), increased bilirubin in the blood and Coomb's testing. The Coomb's test is a test for antigen on the surface of red blood cells and is positive in about two-thirds of dogs with IMHA. A negative Coomb's test does not rule out the possibility of IMHA.
There may come a time when we can identify an underlying cause for every case of immune mediated hemolytic anemia. At present, the best we can do is look for known causes of IMHA, ask about anything else that might precipitate the condition and then make the best possible guess for each individual case.
When immune mediated hemolytic anemia is seen in young dogs it is probably diagnosed as primary, or auto-immune hemolytic anemia, in most cases. Cocker spaniels, poodles, Irish setters and old English sheepdogs are reported to be more susceptible than other breeds in Morgan's Handbook of Small Animal Practice based on a review by Dr. Dodds. It is more common in females than males and it occurs more commonly in the spring, although I did not find any theories on why that happens despite searching several texts. Cats do not appear to have a breed predisposition, based on Dr. Morgan's book.
Cancer is probably the most common primary cause of IMHA. When cancers metastasize they have a tendency to cause an immune response which often leads to hemolytic anemia. This is particularly true of hemangiosarcoma tumors in our practice.
Vaccine reactions are gaining more attention as a primary cause of IMHA but the incidence does appear to be relatively low. Drug reactions are reported to be a possible primary cause and sulfa/trimethoprim, cephalosporin and penicillin class antibiotics have been implicated as possible initiators of IMHA. In cats, blood group incompatibilities between the mother and kittens can lead to immune mediated hemolytic anemia in the kittens (neonatal isoerytholysis) when a Type B queen is bred to a Type A tom.
Infectious diseases can cause IMHA and are probably a common cause in areas in which ehrlichiosis or heartworms are common. Feline leukemia virus may initiate this condition in cats and is one of the causes of cats who are inapparently infected with feline leukemia virus suddenly becoming very ill.
Most of the e-mail and inquiries I have gotten about immune mediated hemolytic anemia revolve around medications that are used on a continuous basis, such as heartworm prevention medications; Program (Rx), Advantage (Rx) and Frontline (Rx) flea prevention medications, methimazole, phenobarbital and even insulin. Whenever IMHA occurs shortly after one of these medications is first used, the owner suspects that it is the cause. This is understandable. People want to know why things happen and it is not very satisfying to hear "I don't know," from the vet. To the best of my knowledge and the best of my ability to search out information there is no correlation between IMHA and heartworm prevention or flea prevention medications at the present time. This is also true of insulin, as far as I can tell. There may be some problems with methimazole (Tapazole Rx) which is used for hyperthyroidism in cats and there may be some problems with phenobarbital, although there isn't much proof in either case. Immune mediated hemolytic anemia existed and was recognized by veterinarians well before any of these medications came to be used commonly in pets. Without a national tracking system for pet diseases it is hard to be sure whether infrequent problems with any medications occur but at present I believe that the newer flea and heartworm preventative medications are not a likely culprit when a pet suffers from IMHA.
Try as I might, I can rarely convince a pet owner that there probably wasn't a cause for the immune mediated hemolytic anemia if their pet dies. Even a thorough autopsy exam still leaves me answering questions about every medication the dog or cat was on, the food it ate and anything else that they might have been exposed to. This is OK, because I would like recognize a pattern if one does occur. I feel sorry for the owners, though. I understand how much they would like a definite answer. It is particularly hard to talk to pet owners when a pet was seen within a week or two of the onset of IMHA and appeared to be normal at that time. This is a rapid onset disease in most cases and it is not unusual to have normal lab work on file from an earlier visit, even a very recent visit, at times. While this is hard to understand for everyone involved, it is no reason to suspect an inadequate examination or faulty interpretation of the earlier lab work.
I do have to tell one story in this regard. Several years ago I began the yearly exam of a young female dog in my clinic. Almost immediately it was apparent that she had very pale gums and slight yellow discoloration to the whites of her eyes. She was scheduled for a heartworm exam during the visit so we drew the blood and checked it, then made some smears of the blood and checked the hematocrit. It was apparent that she was probably suffering from immune mediated hemolytic anemia after examining the blood smears. I explained this to the owners, emphasizing that she could easily die in the next day or so without treatment and suggesting that they forget the vaccination for now and concentrate on her illness. They absolutely refused to believe that I wasn't just saying she was ill to pad my pocketbook. "She's fine," was repeated several times in the exam room and repeated several times more, quite loudly, in my reception area as the owners left. She came back two days later, nearly dead. We were unable to save her. If your vet suspects immune mediated hemolytic anemia it is important to aggressively pursue diagnosis and treatment.
Feline Leukemia Virus Infection
When I said that veterinarians often did not fully understand the diseases that occur in pets, I was referring to myself in the case of feline leukemia virus. The available information on this disease seems to be changing pretty rapidly and I am having a hard time deciding what is true and what is not true about this disease and about the vaccinations we use to try to prevent it.
FeLV is a retrovirus. These viruses live and reproduce inside the cells of their host. Feline leukemia virus does not kill the cells it lives in and thus it can reside in them a very very long time in many cases. For the most part the virus is protected from the immune system while it stays inside the cells. It reproduces by "budding" off of the cell membrane. This does allow the immune system a shot at it and many cats can manage a standoff with the virus in which it is never completely killed off but isn't able to reproduce much, either. These cats are considered to be latently infected. If severe stress to the immune system occurs it is possible for the virus to overwhelm the immune system and become active again.
Kittens who become infected at less than 16 weeks of age are very likely to remain infected and to eventually die from feline leukemia virus or a complication of the infection. Kittens infected after this age have a better chance of mounting a good immune response and eliminating the virus. The immune system gets better at fighting the virus with increasing age, up to adulthood. It is very hard to infect an adult cat with FeLV.
So what are the problems in explaining this virus? Perhaps the hardest one is that a cat may appear to be healthy for several years, living peacefully indoors as the sole pet and then die from FeLV over the course of a few days. These cats may have had negative tests for feline leukemia virus since it can't be tested for when it is latent and not in the bloodstream. Explaining this to a cat owner after their cat has died is a difficult task. It has become a little easier over the last few years because of the educational information available on the human immunodeficiency virus, which also has a latent period before clinical signs appear. Still, this is a hard concept to grasp, especially after a negative feline leukemia test in the cat's past. I do not advocate vaccination for feline leukemia virus when a cat lives indoors, alone. It is sometimes hard to justify this advice when a totally indoor cat patient dies from feline leukemia. I believe that these cats are latently infected in most cases but that does sound like a cop-out when I say it to clients, despite the fact that I truly believe it.
Another major problem right now are vaccine related cancers that occur in cats. These are fibrosarcomas, a particularly aggressive tumor. They are often fatal despite surgical removal and even with surgical removal and follow-up radiation therapy. Current estimates are that these cancers occur in about one in three thousand cats. I have no idea how this estimate was arrived at or its accuracy. Since fibrosarcomas occur naturally it is hard to be sure whether the cancer is the result of vaccination or natural occurrence when it is present. In any case, when a vaccine can cause problems it is a good idea to consider the risk/benefit ratio of the vaccine based on the cat's lifestyle and clinical history. If the cat is likely to be exposed to the virus (multiple cat household, outside cat or indoor-outdoor cat), then it is important to vaccinate as a kitten and probably a good idea to vaccinate again at one year of age. After that it is much harder to decide what to do. At present we are still recommending vaccination every three years for adult cats but that may change over time.
Treatment for feline leukemia virus itself is not possible. Keeping an infected cat indoors, treating any secondary illnesses rapidly and working to keep the cat's life as stress free as possible all help to extend the life span of affected cats. Interferon may be helpful in improving quality of life for some cats but probably doesn't expand life span much or at all. Since there are few veterinarians willing to suggest they have a "cure" for this disease there is a wide-open market for lots of other people to do so. Be careful where you get your advice from when it comes to feline leukemia virus. If vets knew of a cure we'd use it. After all, a vet who could keep all of his or her patients alive would make more money over the long run!
It is important to think about the risk of the disease, the risk of vaccination and your cat's lifestyle when deciding on whether to vaccinate for feline leukemia virus. At present I think it is probably best to vaccinate kittens in most circumstances, with the possible exception of a kitten who will be indoor only in a single cat household. I think the one year booster is important for any cat that will be outdoors even part of the time or that lives with other cats or is exposed to other cats (at shows, for instance). After that, I think it is really hard to make strong recommendations based on the current information available to most veterinarians. It is possible to make a case for not vaccinating after this age since most cats are resistant to infection. On the other hand, the operative word there is "most". Some cats do develop feline leukemia after one year of age, especially when they are exposed to a feline leukemia carrier for prolonged periods of time. Undeniably there is at least a small risk of infection for almost any cat that spends time unsupervised outdoors. At least for now, it is not possible to clearly quantify the risk. Therefore, it is necessary to make an educated guess as to the relative risk of vaccination versus exposure to feline leukemia. You and your vet will have to figure this out for your cat on an individual basis.
New stuff
An "in-house" lab kit is now available to allow veterinarians to determine the blood type of cats and dogs. This is particularly important for cat breeders to be aware of as cats do have a similar problem to the "rH" factor problem seen in human women. If a cat with Type B blood has babies with Type A blood they will often die due to antibodies from the mother against their blood type. Blood typing prior to the need to administer blood is always a good idea, so almost any pet could benefit from this test.
Sometime this summer blood substitutes should be available to veterinarians. This may help resolve one of the hardest issues in veterinary medicine, the lack of widespread availability of blood for emergency transfusions. There are veterinary blood banks but it is costly for veterinarians to purchase blood for emergency use due to its extremely short shelf-life. We tried for a year to keep two pints of canine blood on hand at all times and decided after evaluation of the expense that we would have to charge approximately $400 per dog to break even. Keeping a blood donor dog has worked for us in the past but it is not much more economical. My pets routinely give blood in emergencies but I will not utilize their blood more than once every 6 weeks or so and there are times when I have been unable to find a donor for someone's pet in an emergency. It will be very nice to have blood substitutes for emergencies and I think it will increase the availability of quality care for emergencies involving significant blood loss.
Heavy Metal Dermatitis
Mrs. Gerand lived in a small village near our practice. Her home was among the oldest in the village and her family had lived in it since it was built. She was a Southern Belle, through and through. Her husband had died years before and she lived alone except for her dog, Beau. He was an overweight, overly friendly Boxer who roamed the neighborhood freely. Mrs. Gerand was a little bothered by the neighbor's complaints about Beau's willingness to walk into any house and snack off of any counter, but he was a Gerand and the Gerands had been there first so it wasn't really her concern. The neighbors just had to put up with his idiosyncrasies.
Denial is a strong suit for true Southern women. Ever since the War of Northern Aggression it has been necessary to adjust one's attitude to accommodate the truth without really accepting it and Mrs. Gerand was an expert at this. When I told her that Beau was becoming obese enough to cause health problems she let me know in no uncertain terms that my ability to judge a dog's ideal weight was certainly lacking. It was obvious that I had no idea what a real Boxer should look like and ...... It usually took five or ten minutes to get through the whole tirade and I have a tendency to take a long time listening to a dog's heart with the stethoscope while owners critique my veterinary skills, so I don't know much of what was said beyond the first few sentences. Mrs. Gerand and I developed a relationship in which I examined Beau, decided what was wrong, made one stab at telling Mrs. Gerand and then just prescribed the appropriate treatment explaining only what had to be explained to make it work. Then she told me why I was wrong before going home and then invariably following my directions to a "T".
This worked well for five or six years. Then Beau developed a problem that really strained the working relationship between me and Mrs. Gerand. Beau developed a really odd skin rash. It was mostly confined to the back of his rear legs when Mrs. G first noticed it. There were small scabs scattered around the back of his legs and a couple of them had red swellings around them from infection. I really didn't know what to make of these but sometimes pyoderma (skin infection) in short-haired dogs will present as a scabby skin for no reason. So I prescribed antibiotics and a recheck in a few days if he didn't respond. He healed just fine.
Unfortunately, it was only a month or so later when the skin disease recurred. This time there were scabs all over the top of his back and only one or two on his legs. Thinking that perhaps he had a mite infection that was leading to a bacterial skin infection, I did skin scrapings. Using a scalpel blade, I carefully scraped at the area around a couple of the scabs and put the debris on a microscope slide. When I applied the cover slip I noticed that it didn't settle on the slide due to some hard debris. Which turned out to be a piece of bird shot. It was pretty obvious what was wrong with Beau.
"Someone has shot Beau with bird shot, Mrs. Gerand," I said. To which she replied. "Nonsense, young man. Where did you get that degree you hang on your wall, anyway?"
I struggled to convince Mrs. G. that Beau had been shot with bird shot, to no avail. I took an X-ray, out of frustration, and showed her the many small pieces of lead in his skin. I showed her the piece I found on the slide. It didn't matter. No one could possibly shoot Beau. He was too nice a dog and he was a member of the Gerand household. No one would dare.
I sent Beau home on antibiotics. He recovered uneventfully again. He returned in three weeks this time, though. The scabs were now all over his back legs again. Mrs. Gerand was becoming tired of my inability to diagnose and prevent this condition. She let me know. In fact, she was loud enough this time that most of the clients in the waiting room were made aware of her opinion of my competence. I knew that I had to do something to prevent the recurrence of this catastrophe.
I walked to the back room and sat down. Finally, it occurred to me what to do. I told Mrs. Gerand that I had found the cause of Beau's problems. I assured her that together we could cure Beau, if she was willing to work very hard at it. It would be necessary to take him for walks on a leash only. No more running the neighborhood because we just didn't know where he going that he was exposed to this terrible problem. Even though we could cure the symptoms with ease, eventually it was going to be bad for him to continue to be exposed to the problem. Mrs. Gerand was now pretty intrigued. In fact, I don't think she ever listened to me for as long at one time as she was now.
I told her that Beau's problem was "Heavy Metal Dermatitis". I wrote it on his chart in the "Final Diagnosis" box. She was thrilled. As far as she could remember, no one she ever knew had a dog with heavy metal dermatitis. Beau wasn't allowed to roam the neighborhood anymore. After all, who knew where he was getting exposed to this heavy metal? Mrs. G. didn't have to deal with the fact that someone in the neighborhood was shooting bird shot at Beau because that wasn't the problem after all. If she just walked him on a leash and kept him at home he was going to be fine.
She kept on walking him until she got too frail to keep up with a big dog and her niece took him home with her. I sent our records to Maryland with him. I hope that the vet there didn't think I was totally nuts when he or she read the diagnosis on the chart.
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