2016 SPRING: Canine Demodicosis | Color Dilute Alopecia | Post-Clipping Alopecia | MDR1 Gene Mutation – Toxicity | Hyperthyroidism and Kidney Failure | Derm News | Pearls from ACVIM Forum 2015 | City in the City | Meet Judy Seltzer, BVetMed, MRCVS, DACVD
Canine Demodicosis: Review and Exciting News
Canine demodicosis is a cutaneous disorder that predisposes dogs to develop secondary infections of the skin. We are beginning to understand a little more about this parasite with the advent of modern microbiologic techniques, but discoveries about new treatments tend to be serendipitous, as these mites cannot be grown in vitro.
In the past, we recognized what we thought were three distinct species of mites: D. canis (the traditional mite we find in the hair follicles of dogs), D. injai (the long-tailed mite we associated with seborrheic conditions), and D. cornei (the short, stubby mite similar to D. gatoi in cats). Molecular analysis has shown that while D. injai is a separate species, but D. cornei is just a different morphologic form of D. canis.
Dobby upon presentation, after one month on Nexgard and after two months of treatment
These products will provide not only effective treatment, but also easy maintenance for dogs with chronic demodicosis, while providing great flea and tick control!
We recognize localized demodicosis as a disorder that can be associated with spontaneous resolution. Generalized demodicosis in young dogs has been attributed to a genetic predisposition, and for that reason, it is recommended that these dogs be neutered.Neutering also prevents the relapse of the mange often associated with estrus in females. Adult onset demodicosis suggests the development of an underlying disorder that changes the skin biology or skin immune system in such a way that mites overgrow. We look for endocrine diseases, such as hyperadrenocorticism or hypothyroidism; any systemic disease that weakens immune function, including neoplasia; and the use of medications including steroids and possibly oclacitinib, whose use can be associated in some dogs with mite overgrowth.
It is important to recognize that for some dogs, we don’t find an underlying cause. We simply treat the disease and recommend maintenance therapy to prevent relapse. A perfect example is adult onset generalized demodicosis in shih tzus. These dogs often develop deep pyoderma, particularly in their feet. Any adult shih tzu that develops pyoderma of the feet, even if they have a past history of atopic dermatitis, should be evaluated for demodicosis. We find that hair plucks are very effective for this purpose.
The most exciting news about canine demodicosis is the discovery that the new isoxazoline flea and tick control products, afloxalaner (Nexgard®) and fluralaner (Bravecto®) appear to be very effective in treating demodicosis in dogs. When used according to the label instructions for flea and tick control, these products appear to kill demodex mites very quickly and result in rapid resolution of the disease. There is one publication available for Bravecto at this time, but we anticipate that more will be published on both medications in the foreseeable future. With a treatment protocol of Nexgard every 30 days, we’re finding that after one dose, the mite counts are dropping from adults, juveniles and eggs too numerous to count to 1-2 dead mites in one month! Truly amazing.
Reference: Fourie et al. Efficacy of orally administered fluralaner (Bravecto) or topically applied imidacloprid/moxidectin (Advocate) against generalized demodicosis in dogs. Parasites and Vectors (2015) 8:187.
Color Dilute Alopecia
Many of us know them as blue or fawn Dobermans. Other breeds such as dachshunds, German shepherds and great Danes are also commonly affected. Afflicted dogs demonstrate lighter hair coat coloring than typical for their breed, such as silver instead of black, or fawn instead of brown. Their unusual hair color makes them popular with pet owners, at least when first adopted. Unfortunately, many of them will develop skin and hair coat problems when they reach 6 months to 3 years of age. This condition, known as color dilute alopecia, is believed to be inherited and is the result of mutations in multiple genes.
The severity of the skin condition that develops in dogs with color dilute alopecia varies. Most dogs demonstrate a patchy alopecia over the dorsal trunk as the hair follicles become dysplastic. Abnormal clumping of melanosomes within the hair shafts causes the shafts to fracture and break. Many dogs will also develop underlying comedones, seborrhea and secondary bacterial folliculitis. A skin biopsy of the affected areas is required to make a definitive diagnosis.
“There is no cure for the cutaneous manifestations of color dilute alopecia. The goal of therapy is to minimize discomfort in the pet by controlling infection and reducing seborrhea,” says Dr. Katie Rook. Fatty acids and epidermal health products are typically prescribed. Antibiotics can be used to control secondary infections. Melatonin may improve hair growth. Unfortunately, treatment of color dilute alopecia can be frustrating and is lifelong. Therefore, should you have a patient with a chronic skin condition such as color dilute alopecia, consultation with one of our dermatologists is recommended.
What Causes Post-Clipping Alopecia?
We have all run into what appears to be an otherwise healthy dog who has failed to regrow hair within a reasonable period of time after a surgical or sterile clipping. In some cases, the hair regrowth appears to occur as tufts. Why does this occur? According to our dermatologist, Dr. Jill Abraham, there are a number of potential reasons for post-clipping alopecia:
- Sometimes these pets have an occult endocrinopathy such as hypothyroidism, hyperadrenocorticism or abnormal sex hormones, which interferes with hair growth.
- Other pets are receiving a medication, corticosteroids being the classic one, which slows hair growth.
- The clipping may have occurred during a normal but prolonged telogen stage of hair growth when many of the hair follicles are in a deep slumber for months to even years.
- It has been suggested that perfusion of the hair follicles is decreased as the peripheral blood vessels constrict in response to decreased skin temperatures at the site of clipping. There is less blood flow to stimulate hair growth.
- An underlying primary skin condition, such as yeast or mange infection, could also contribute to slow hair growth.
The diagnostic evaluation in these dogs should include a thorough history inclusive of medication exposure and any additional clinical signs noted by the pet owner, a general health blood profile, endocrine hormone testing, skin scraping and dermatophyte testing, and then possibly skin biopsy. Melatonin supplement may help stimulate hair growth in some idiopathic cases.
Our dermatologists are available to discuss post-clipping alopecia or any other skin condition you may have questions about.
Potential Toxicity? Don’t Forget the Patient
When it comes to being suspicious for the presence of a toxic reaction, you shouldn’t just look at the potential chemical exposure. You also have to consider the health status of the patient. The presence of an underlying problem in a pet can change what would typically be a safe chemical exposure into a life threatening exposure. What would be a good example of this? How about the presence of a MDR1 gene mutation in some herding breeds.
What is the MDR1 gene mutation?
The development of ivermectin to prevent heartworm disease and treat other parasites was a tremendous step forward for the veterinary profession. It did not take long, however, to realize that in collies recommended doses of ivermectin, found to be safe in other breeds, caused severe neurologic signs. Subsequent research determined that many collies carried an inherited defect in their multi-drug resistance (MDR1) gene. This gene encodes for P-glycoprotein. P-glycoprotein is located in the cell membranes of the liver, pancreas, intestines, kidney and brain capillary endothelium. It functions to bind and actively transport certain chemicals that have leaked into the cell cytoplasm out of the cell. Collies who possessed the MDR1 gene mutation did not produce adequate P-glycoprotein concentrations needed to remove the ivermectin that leaked into their brain cells. The excessively high concentration of intracellular ivermectin was responsible for the abnormal neurologic signs.
P-glycoproteins are responsible for clearing a number of other chemicals and drugs from within susceptible cells. A list of drugs to be concerned about can be found on the Washington State University college of veterinary medicine’s website. The administration of these drugs to dogs with the MDR1 gene mutation has been reported to cause variable and potentially severe side effects including neurologic signs, gastrointestinal signs and myelosuppression. :
A number of breeds have been shown to potentially carry the MDR1 gene mutation, namely collies, Australian shepherds, Shetland shepherds (shelties), old English sheepdogs, and long-haired whippets. Infrequently, the defect has been found in other breeds. The disorder is inherited as an autosomal recessive gene. There is a screening test to confirm the presence of the mutated MDR1 gene available at Washington State University’s college of veterinary medicine. Test results indicate if the dog carries two, one or no copies of the mutated gene. Even heterozygous dogs may show some susceptibility to toxicity.
What should you do if you have a breed that carries the MDR1 gene mutation?
It is safest to avoid the drugs to which the dog may be sensitive. If you must use a potentially toxic drug, the dose should be decreased by 50% in homozygous dogs and 25% in heterozygous pets. Pet owners should be informed of the associated risks of treating the patient.
Did you know?
The presence of P-glycoprotein in some cancer cells is likely responsible for rendering them multidrug resistant. Researchers are looking for ways to inhibit the action of P-glycoproteins in cancer cells to improve the efficacy of anticancer medications.
Hyperthyroidism and Kidney Failure – a Concern?
Both hyperthyroidism and kidney failure are commonly seen in older cats. Occasionally, they may be present in the same patient. Unfortunately, hyperthyroidism can mask the signs and abnormal laboratory findings in cats with kidney failure making it difficult to confirm the presence of both conditions.
How does hyperthyroidism affect the kidney?
Thyroid hormone appears to enhance the responsiveness of B-adrenergic receptors in the heart leading to increased heart rate, increased left ventricular contractility, and subsequently increased cardiac output. Thyroid hormone also appears to act on smooth muscle cells within the peripheral arteries causing relaxation and decreased peripheral vascular resistance. The decrease in arterial filling volume induces activation of the renin-angiotensin-aldosterone system, which stimulates increased sodium reabsorption by the kidneys and secondary water retention. The subsequent increase in blood volume increases blood return to the heart (increased preload). The increase in preload in combination with the decreased systemic vascular resistance also increases cardiac output.
An increase in cardiac output increases renal blood flow and, in turn, the glomerular filtration rate (GFR). BUN and creatinine are cleared more effectively from the body. The concurrent presence of kidney failure in cats with concurrent hyperthyroidism as assessed using BUN, creatinine, or even tests on GFR, is masked.
Now if you correct the hyperthyroid state, the patient’s cardiac output, and subsequently the GFR, return to normal. Kidney values once again increase. Azotemia has been reported to occur in 15-49% of hyperthyroid cats after treatment, despite the type of treatment.
Can you predict which cats will develop azotemia posttreatment?
Studies to date have failed to identify a marker that will identify those hyperthyroid cats with concurrent kidney failure. Pretreatment values for BUN, creatinine and even urine SG have failed to be reliable predictors for the development of posttreatment azotemia.
How long after treatment before azotemia would become evident?
Studies have indicated that the GFR will decrease during the first 2-4 weeks after treatment.
What is a methimazole trial?
Because it is the correction of the hyperthyroid state and not the type of treatment that unmasks the azotemia, it is possible to get a preview of the cat’s true kidney function, prior to curing the thyroid condition with radioactive iodine by performing what has been termed a methimazole trial. To perform a trial, administer methimazole with the goal of dropping thyroid hormone levels into the normal range. Once thyroid levels have normalized, blood tests performed 2-4 weeks later would be expected to demonstrate the BUN and creatinine values that you would see after radioactive iodine therapy.
When would a methimazole trial be performed?
We typically recommend the trial be performed in cats 14 years of age or older and in those cats with any suspicion for concurrent kidney disease based on the patient’s history, exam findings and lab test results (significantly elevated BUN value and isosthenuria). Why do we perform the test? It’s all about the owners’ expectations. We feel it is important for owners to be aware that concurrent kidney insufficiency is present prior to encountering the expense of radioactive iodine treatment.
What if kidney failure develops after thyroid treatment?
The good news is that, despite the development of posttreatment azotemia, most cats continue to do fine. In one study, the median survival time in cats treated for hyperthyroidism that developed azotemia posttreatment was similar to treated cats that did not develop azotemia (>500 days). The treatment for kidney failure includes ensuring hydration, feeding an appropriate diet, and addressing the complications of kidney disease such as hypertension.
Is there a preferred treatment for hyperthyroidism?
Radioactive iodine therapy is considered the most consistent and predictable means for curing hyperthyroidism in cats. It is technically simpler than other treatment options and involves only a single injection of the liquid chemical. There is no need to administer tablets or creams for the life of the cat or to feed an exclusive diet. Surgical thyroidectomy carries the risk of damaging the parathyroid glands. Meanwhile, poor client compliance, inadequate dosing, a risk for side effects, and the expense of the medication and recommended thyroid monitoring, associated with the use of methimazole are additional reasons to consider treating hyperthyroid patients with radioactive iodine. Another point to be made is that the stress, on both owner and cat, of twice daily medication administration can cause damage to the human animal bond. In one study, hyperthyroid cats treated with radioactive iodine were shown to live longer than those treated with methimazole despite the radioactive iodine-treated population actually being older in age.
Dr. Jean Ferreri treats hyperthyroid cats with radioactive iodine at BluePearl Midtown every month. Feel free to call her if you would like to discuss a patient that may benefit from this treatment.
What’s New in Dermatology?
Gone are the days of mitaban dips, doramectin injections and daily oral ivermectin for months on end. Two new weapons have emerged in the evolving war on demodicosis: Merial’s Nexgard® (afoxolaner), and Merck’s Bravecto® (fluralaner). Veterinary dermatologists have been discussing treatment successes they are seeing following once-monthly administration of Nexgard, or once every 2-3 months of Bravecto. Currently, as with doramectin and ivermectin, treatment of demodicosis with these drugs is extra label; thus, pet owners should be informed of this prior to prescription. The serious adverse reactions reported with ivermectin and/or doramectin (i.e. blindness, ataxia, possible death in dogs with MDR1 gene mutations) were not reported in well-controlled field/laboratory studies. Common side effects observed include GI upset (vomiting, inappetence, diarrhea, flatulence), polydipsia and/or lethargy. Monitoring of treatment progress with skin scrapings every 4-6 weeks is still recommended, and continuation of treatment until achieving two negative scrapings 4 weeks apart remains the standard of care.
As we know, Apoquel® (oclacitinib) has been popular during the last two years. While Zoetis is challenged to keep up with demand for this ‘miracle’ drug, veterinary dermatologists are currently reporting fair to excellent control of atopic symptoms in approximately 65% of patients. When prescribing Apoquel, it’s important to understand that this drug is not without limitations and/or adverse effects, including labeled for use in dogs one year and older, increased incidence of papillomatous growths, development of urinary tract infections, weight gain, elevations in liver enzymes, blood dyscrasias, and rarely, acute death. Furthermore, it is important to perform a full medical workup to rule out other possible causes for pruritus, such as bacterial pyoderma secondary to demodicosis, cutaneous lymphoma, or other non-allergic pruritic dermatoses, as failure to do so can result in further progression of the disease. Clinical improvement of allergic otitis is lacking. Apoquel may be an excellent secondary drug for managing symptoms of atopy in the initial stages of immunotherapy; however, it should not be seen as a replacement.
Pearls from the ACVIM Forum 2015
Can you trust the urine SG (USG) in dogs with glucosuria?
A recent study evaluated the effect of adding increasing concentrations of glucose to urine samples with varying starting USGs. Predictably they found that the lower the starting nonglucosuric USG, the greater the effect adding glucose had on the subsequent USG. Furthermore, the higher the concentration of glucose added to the urine sample, the greater the change in the subsequent USG. However, the addition of even higher concentrations of glucose to urine samples with low USG failed to cause clinically significant changes in the final USG. Researchers concluded that the presence of glucosuria did not interfere with the assessment of renal concentrating ability. (Behrend et al)
Are all antiemetic medications the same?
Well that depends on your goal. Gastric antral motility (contractions per minute) was measured before, during and hourly after the feeding of a meal in normal dogs given metoclopramide, maropitant, dolasetron or saline 1 hour prior to feeding. Researchers found that all three medications increased gastric motility prior to feeding and then intermittently during hourly measurements performed for 7 hours after feeding. Only metoclopramide increased motility at all time measurements. If the goal is only to inhibit nausea then all three medications can be effective. However, if increasing gastric emptying is also the goal, then metoclopramide may be your drug of choice. (Bogard et al)
FROM THE MEDICAL DIRECTORS
New Doctors and CE in the City
Spring is upon us and with that comes several exciting additions to BluePearl New York. We are pleased to announce the expansion of our dermatology, internal medicine, oncology and surgery services. Dermatologist Judy Seltzer will be joining us in mid-April. Get to know her in our SNIFF interview in this issue of Companion. Dr. Alexis Cistola joined our internal medicine service in Queens this past month. Dr. Andrew Goodman joined Dr. Kelson Danielson in March, allowing for seven day per week surgery coverage in Brooklyn. Double boarded in radiation oncology and medical oncology, Dr. John Farrelly will be seeing cases out of BluePearl Midtown this May.
We would like to take this opportunity to remind you that the eighth annual CE in the City will be held on Saturday, April 16, at The Westin New York Grand Central.
You can earn up to eight hours of NYSED approved CE credit for only $35. All of the money we raise will be donated to NY SAVE. So come and join us for a day of good conversation while giving to a local charity run by your colleagues. For more information, email Dr. David Wohlstadter at email@example.com.
Marc Greenberg, DVM, DACVS
Timothy Rocha, DVM, DACVIM-Oncology
Welcome our new dermatologist…
Judy Seltzer, BVetMed, MRCVS, DACVD
Dr. Judy Seltzer comes to BluePearl after practicing in Long Island for 6 years. She completed her residency at the University of Florida, a dermatology internship at Red Bank Veterinary Hospital in NJ and a rotating internship at the Center for Specialized Veterinary Care in Long Island. She earned her veterinary degree from the Royal Veterinary College in London.
Skilled in all aspects of dermatology and allergy, Dr. Seltzer especially enjoys treating environmental allergies and immune-mediated dermatological diseases. During her free time, she enjoys traveling around the world and spending time with her four cats, Huxley (named after a layer of the hair follicle), Kabuki, Katt and Allie.
Judy Seltzer, BVetMed, MRCVS, DACVD
What keeps you interested in cases day after day?
I really enjoy the long-term relationships I make with the clients and patients. So many of my cases are allergy related, meaning they will likely need to be managed for the rest of their lives. Even though there are some frustrating days, it is so nice to see long-term patients showing improvement while they are under my care. I love looking at before and after pictures and seeing how far my patients have come.
How do you like to work with the primary care veterinarian?
I have always maintained a great relationship with the referring veterinarians in my community. I provide them with reports after each appointment and keep in contact with them on the phone when significant changes to the treatment protocol are being made. If the owners prefer to return to their primary care veterinarians for follow-up care, I am happy to help them manage the case as best as I can. I find it extremely important for my clients/patients to maintain a close relationship with the primary care veterinarians to monitor the overall wellness of the pet. Additionally, I make myself available to answer any questions referring veterinarians have about our mutual cases or cases they just want some extra advice on.
How do you go about easing the concerns of an upset client?
Our pets are members of our family; they are our children! I am open and honest with clients, explain my thought process and recommendations thoroughly and give them time to ask as many questions as they’d like. I want them to feel comfortable with me and the decisions they are making. I encourage them to contact me if they have questions after they leave the appointment. If finances are a concern, I make sure we modify a treatment plan to make both the client and patient comfortable.