What Does a Veterinarian Do When a Pet With a Complicated Medical History Gets Sick Again?

This article originally appeared on Dr. Mahaney’s The Daily Vet column on PetMD as What Does a Veterinarian Do When a Pet With a Complicated Medical History Gets Sick Again?

Since November’s National Pet Cancer Awareness Month is ending, this will be the last of my cancer-related posts in this column for the time being.For those of you petMD readers who aren't aware, my dog Cardiff has endured three episodes of typically fatal immune mediated hemolytic anemia (IMHA) and one bout of cancer (T-cell lymphoma) in his nine years of life.Having a pet that has gone through both immune mediated (“autoimmune”) disease and cancer is a challenge for any owner or its overseeing veterinarian, as there always is the concern that either or both illnesses will recur.Since Cardiff finished his course of chemotherapy for lymphoma this summer, he’s been feeling energetic, eating with a normal appetite, enjoying challenging hikes at home in Los Angeles, and lakeside sprints in Massachusetts. Yet, just when we thought everything was going great, his day-to-day health started to decline this fall. What is Currently Going on With Cardiff’s Health? Cardiff’s latest health issue started with non-life-threatening clinical signs that wouldn’t normally cause significant concerns for the typical pet owner. Of course, Cardiff isn’t an average pooch and I’m a highly-informed pet owner, so any deviation from his normal is highly scrutinized for potential causes and outcomes. Cardiff's clinical signs included: Anorexia — decreased appetite (partial anorexia in Cardiff’s case, as we were still able to get him to eat some food) Lameness — limping (alternating between right and front limbs in Cardiff’s case due to osteoarthritis in his toes) Lethargy — lower energy, sleeping more, exercise intolerance, etc. Partial anorexia, lameness, and lethargy were also the main clinical signs Cardiff exhibited during his most recent IMHA episode in 2009. The lameness doesn’t fit the bill for his cancer, which manifested as a tumor on a loop of small intestine that prevented food and fluid from appropriately moving in a downward direction. Due to the intestinal tumor, Cardiff was having partial anorexia, lethargy, and regurgitation of the food (seemingly undigested) he had eaten hours before. Of course, anorexia and lethargy are also consistent with lymphoma, other cancers, or a variety of other diseases (glandular problems, infection, toxicity, etc). In Cardiff’s case, I was left with another challenging puzzle to solve before determining the most appropriate course of treatment. How Was It Determined That Cardiff Was Having IMHA Again and Not Cancer? Since the completion of his chemotherapy in July 2014, I’ve been running routine blood screening on Cardiff approximately every 30 days. The good news in working up his latest bout of illness is that his latest blood tests weren’t overly remarkable. With IMHA, the red blood cell, hemoglobin (iron component of red blood cells that transports oxygen), and hematocrit (percentage of the blood made of red blood cells) levels are those values that indicate a problem when they are low. Of course, there’s a wide range of normal for these values. So, a pet may not yet be anemic (low red blood cell count) but could be having an emergence of IMHA, as not enough red blood cells have yet been destroyed to cause the red blood cell level to be low. Seeing all three tests appear within normal limits (or WNL, as we veterinarians like to say) in Cardiff’s case is a positive finding, but it doesn’t mean that the patient is normal and that there’s not a disease process occurring. Another hallmark of hemolytic anemia (where a disease process destroys red blood cells) is elevated bilirubin, which causes a distinct yellow appearance to the serum (the parts of the blood not made up of red/white blood cells and platelets). When whole blood is centrifuged (spun down) in a serum separator tube, the serum rises to the top and all other blood components are displaced to the bottom of the tube. Red blood cell destruction or liver and gall bladder diseases cause elevated bilirubin, which lends a distinct, bright-yellow to orange appearance, known as icterus, to the serum. Additionally, the sclera (white of the eye), gingiva (gums), and skin of the inner ear flaps and other ares of the body having less hair can also take on a characteristic yellow appearance that we veterinarians never like to see when evaluating our patients. Seeing Cardiff’s low normal red blood cell level and normal bilirubin certainly provided some sense of relief, but during his initial stages of his previous bouts of IMHA there also were no significant abnormalities. Ultimately, Cardiff’s red blood cell levels then started rapidly dropping and his bilirubin increased. One hallmark of both Cardiff’s IMHA and cancer has been a reduced T4 (baseline thyroid level), which can be low-normal or low due to a phenomenon called euthyroid sick syndrome. This means that a pet isn’t hypothyroid, but there’s another disease process (infection, inflammation, immune-mediated disease, cancer, etc.) that is causing the level to falsely appear low. Further thyroid testing can differentiate among hypothyroidism and euthyroid sick syndrome. So, besides IMHA, Cardiff could be having a reemergence of lymphoma or even another cancer that was suppressing his T4. The deeper diagnostic process to further evaluate Cardiff’s current issue then began. Due to his previous history of intra-abdominal cancer, Cardiff underwent chest, abdominal, and front limb radiographs (X-rays) and abdominal ultrasound (thank you Southern California Veterinary Imaging). Fortunately, none of Cardiff’s imaging showed any evidence of cancer nor other major concerns, so the highest differential diagnosis was IMHA and the treatment process began. What Kind of Treatment Does Cardiff Need to Treat His IMHA? Where are multiple aspects to Cardiff’s IMHA treatment, with the primary components being: Immunosuppression — Drugs are used to suppress the immune system from attacking its own tissues: red blood cells in Cardiff’s case. In Cardiff’s case, I’m using Prednisone and Azathioprine (Imuran) as he’s shown a favorable response to both medications before. The ultimate goal is to taper down and discontinue the Prednisone while maintaining the non-hemolytic state with Azathioprine every 48 hrs (every other day). Blood Transfusion — To permit body tissues to oxygenate in the face of the red blood cells being destroyed, a whole blood or red blood cell transfusion is needed. Cross-matching the donor to the recipient is essential to minimize potentially life-threatening transfusion reactions. Management of Side Effects — Prednisone is a steroid with many side effects besides immunosuppression, including polydipsia, polyphagia, polyuria (increased water consumption, appetite, and urine output, respectively), gastrointestinal inflammation/ulceration, liver inflammation/enlargement, susceptibility to opportunistic (secondary) infections. Azathioprine is a purine analog that also helps to control the immune response and has many fewer side effects than Prednisone, but it can cause pancreatitis (inflammation of the pancreas). Supporting Whole Body Health — Cardiff takes supplements and herbs to support all body systems, including: Rx Vitamins for Pets Nutrigest (probiotic and digestive tract support) Honest Kitchen ProBloom (dehydrated goat’s milk with probiotics and digestive enzymes) Functional Nutriments Nutrocept (joint-supporting glucosamine and other ingredients that augment whole-body function, which is a maintenance version of the Apocaps he took during his cancer treatment) Nordic Naturals Omega 3 Pet (fish-oil based omega 3 fatty acids that have a natural anti-inflammatory effect) Nutramax Denamarin (milk thistle/SAMe combination to enhance the liver’s detoxifying function) TCVM Herbal Wei Qi Booster (herbal combination that moves blood and has an anti-cancer/anti-inflammatory/anti-bacterial/anti-viral effect) Vitamin B12 injections (for digestive and immune system support) Iron injections and oral supplementation (iron is the basic building block of hemoglobin) How Can a Pet Owner Help Prevent IMHA Development and Recurrence? The management of diseases like IMHA is complicated and expensive, so the best strategy is to reduce immune system stimulation, including: Avoiding stinging-insect or other hypersensitivity (“allergic”) reactions — bee stings, snake bites, exposure to environmental allergens/toxins, and consumption of certain foods all can activate the immune system and should be avoided as much as possible. Preventing or resolving inflammation and infection — joint, skin, intestinal, and other body system inflammation and infections (periodontal disease, bacteria from fleas/ticks, etc.) can trigger an immune system response. Therefore, minimizing the presence of such immunostimulants is key to IMHA management. Determining alternative strategies to vaccinations — Although vaccinations are important to create immunity to infectious diseases, the immunity often carries on longer than the recommended booster time. As single or multiple vaccination can cause a vaccine associated adverse event (VAAE), it’s best that owners who have a pet with an immune system disease like IMHA, cancer, or others, work with their veterinarians to determine an appropriate alternative strategy (vaccine antibody titers via VacciCheck, lifestyle modification, etc.). Why Did Cardiff Have a Recurrence of IMHA? In Cardiff’s case, my strongest inclination as to why his IMHA recurred was the fact that I did not start him back on the immunosuppressive drug Azathioprine. This drug was seemingly the key to keeping him from developing an over exuberant immune system for a four-year stretch from 2009-2013. During this time, Cardiff took Azathioprine at a bodyweight appropriate dose on an every 48 hour (every other day) frequency and tolerated it extremely well. When Cardiff was diagnosed with lymphoma in December 2013, I elected to discontinue his Azathioprine, as immunosuppressive drugs can inhibit the surgical recovery process and he needed to heal from the surgery to remove his small intestine tumor. The extensive course of chemotherapy served also as an immunosuppressant, so providing him with Azathioprine was deemed unnecessary at the time. Once he was done with his chemo, I speculated as to whether we should again start the Azathioprine. Both Cardiff’s internal medicine specialist and oncologist hadn’t previously cared for a patient having the “double whammy” of diseases like Cardiff, so they were unsure as to what was the best option for him. I felt taking the watchful waiting approach seemed appropriate considering all Cardiff had been through, and for some time this approach seemed to be working. Yet, as soon as Cardiff started to again show his clinical signs of IMHA I found myself regretting the decision to not put him back on Azathioprine. Needless to say, after one transfusion of red blood cells, high doses of Prednisone, daily treatment with Azathioprine, ongoing whole-food diet feedings, and the combination of immunosupportive supplements and herbs, he’s nearly back to normal. He’s gained some weight from his Prednisone, which has been drastically tapered, and recently suffered a bout of pancreatitis (either from his Azathioprine or being overindulged at a temporary caretakers house), but he’s pretty much the Cardiff of his pre-cancer days. Now I just need to continue weekly blood testing, schedule a follow up abdominal ultrasound ( at three month intervals), continue to taper and discontinue his Prednisone, keep him on Azathioprine, appropriately modify his supplements and herbs, and watchfully wait.