2016 SPRING: Canine Demodicosis I Reverse Sneezing | Atopy | Pain Management for Cancer | Unresectable Mast Cell Tumors | Feline Hemotropic Mycoplasmosis | Feline Anemia Trial | Meet Dermatologist Marlene Pariser
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.
We recognize localized demodicosis as a disorder than 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. Dogs can be treated with Nexgard every 30 days. 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.
These products will provide not only effective treatment, but also easy maintenance for dogs with chronic demodicosis, while providing great flea and tick control! Please feel free to contact us with any questions.
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.
Parasite. 2016;23:14. Pub 2016 Mar 24. Efficacy of oral afoxolaner for the treatment of canine generalised demodicosis. Beignet F, Halos L, Larsen D, de Vos C.
Sneezing in Reverse
Nothing seems to freak out owners more than a reverse sneeze. Owners seem convinced that their dog is suffocating. Attacks can last minutes and are frequently recurrent. It’s hard to strike a serious tone with owners as we explain how harmless the condition typically is. So why does it occur?
Reverse sneezing has also been termed paroxysmal respiration.
A reverse sneeze is the equivalent of us sucking mucus located in our nasopharynx (post-nasal drip anyone?) back into our throat during a cold or severe allergy attack. Whereas we might spit the mucus out, dogs will typically swallow it. In humans it is primarily a voluntary action, whereas in dogs it appears to be more of a reflex triggered by anything that causes irritation in the nasopharyngeal area. Episodes are acute in onset. Dogs extend their head and neck forward and then start with violent inhalations through their nostrils causing a snorting sound. Dogs remain conscious during the episode. For unknown reasons, beagles seem to be afflicted with the condition more often than other breeds.
For some dogs, the trigger is a nasal or sinus infection or inhalation of a simple irritant. Allergies, foreign bodies and even tumors can trigger the reflex. In most cases the source of the episode is quite benign. The attacks will stop even without treatment. Should the episodes frequently recur or be accompanied by other signs of upper respiratory disease, then further investigation of the condition would be in order. Imaging of the nasal passages, sinuses, nasopharynx and oropharynx with radiographs, laryngoscopy, endoscopy or even a CT scan may be required. Symptomatic therapy utilizing antihistamines, corticosteroids and nasal flushes can prove effective in many cases.
Atopy: Itching To See a Dermatologist
There are many causes for pruritus in dogs, most notably infectious disease, immune disease and various allergies. One of the most common and frustrating conditions to deal with is atopy.
“Atopy, or atopic dermatitis, is an extremely common and frustrating disease process that can be difficult to diagnosis due to symptom overlap with similar diseases. It can also be frustrating to treat because there is no ‘cure.’ Treatment requires lifelong management of symptoms using a multi-modal approach with topical, anti-inflammatory and immunosuppressive medications and allergen-specific immunotherapy while managing secondary infections,” says Marlene Pariser, DVM, DACVD.
The inflamed inguinal region in a Westie with atopy
Intradermal skin test results are used to identify the allergens responsible for the atopic reaction.
Atopy is believed to be an inherited condition commonly seen in many breeds. Signs of atopy can be seen in dogs as young as three months of age, although most dogs first demonstrate signs when they are one to three years of age.
Pets predisposed to atopy develop excessive IgE antibody concentrations when the immune system is exposed to allergens such as tree and grass pollens, molds and dust mites. The skin is the main route of sensitization. Upon continued exposure the inciting allergens bind to IgE antibodies located on mast cells and Langerhans cells in the dermis, causing the release of inflammatory mediators. Signs of atopy such as pruritus and erythema result from the effects of these mediators. The allergic load required to induce signs of atopy likely varies with the individual pet. The presence of concomitant conditions such as bacterial and yeast infections contribute to the severity of the clinical signs.
Typical signs of atopy include itching and scratching involving the paws, face, ears, axillary region, inguinal region and forelimbs. Occasionally respiratory signs of coughing and sneezing will be seen. Signs may initially be seasonal; however, it is not uncommon for signs to become more severe and year-round over time.
The diagnosis of atopy is based on the patient’s history, breed and clinical signs. Testing is typically performed to exclude other skin conditions such as flea allergies, food allergies and skin infections.
The best long-term solution for controlling atopy is allergen-specific immunotherapy (ASIT), which was formerly called hyposensitization. ASIT is now available in both an injectable and oral form. ASIT will prove effective for reducing the severity of clinical signs in approximately 70-80% of patients. To identify the likely allergens responsible for the atopic reaction, intradermal testing, in which small amounts of potential allergens are injected into the dermal layer of the skin, is performed. Intradermal testing remains the ‘gold standard’ for identifying airborne allergens in both the veterinary and human medical fields. By contrast, blood testing has proven to be a less effective methodology.
To perform hyposensitization, small volumes of the specific allergens to which the patient tested positive are injected subcutaneously into the patient. Pet owners are taught how to administer these injections at home. These injections reduce the inflammatory response by altering both cellular and chemical reactions to the allergens. The effects of hyposensitization are typically seen within the first four months of therapy. Some patients may take up to a year to demonstrate a response. Injections are continued for the life of the pet.
Don’t let that itchy dog keep your client up at night. Give a call to a member of our dermatology team.
Pain Management for Cancer Patients
The management of pain in cancer patients is among our highest priorities. Several options exist for pain management.
Non-steroidal anti-inflammatory drugs [NSAIDs]
NSAIDs are an essential part of most analgesic regimens. There are both non-selective (COX-1 and COX-2) and COX-2 selective families of NSAIDs. Not only do these drugs reduce mild to moderate pain, they are inexpensive and generally well tolerated. Some COX inhibitors may also have anti-tumor properties by promoting apoptosis or reducing angiogenesis. Potential adverse effects are mainly gastrointestinal related, and rarely, nephro- or hepatotoxicity. Periodic physical examination and monitoring of hematocrit, reticulocyte count (even if not anemic), chemistry profiles, and urinalysis is advised. As a general rule, NSAIDs should never be combined with glucocorticoids due to additive toxicities.
Short-acting steroids at anti-inflammatory doses may decrease mild inflammation and pain associated with certain tumors, such as mast cell tumors. Steroids may also be indicated in the treatment of lymphoid neoplasms (lymphoma, multiple myeloma, plasmacytoma, and leukemias) and myelomonocytic/histiocytic malignancies. For two reasons we recommend using steroids only after a definitive diagnosis has been made: premature use of steroids may complicate the establishment of a definitive diagnosis and accurate tumor staging; and, although controversial, they may negatively impact the prognosis if definitive therapy is employed. The potential adverse effects of short term and chronic steroid use include GI ulceration, PU/PD, polyphagia, panting and iatrogenic Cushing’s disease.
Opiates, indicated for patients with moderate to severe pain, are commonly used in hospitalized patients. Buprenorphine, a potent injectable opiate, is commonly used to treat cats and small dogs. The parenteral preparation, when given per os, is absorbed transgingivally. The volume required for this route of administration makes it impractical to use in medium or larger-breed dogs. Carefully selected patients may benefit from fentanyl patches, which provide approximately 4-5 days of pain relief. Tramadol, an inexpensive, orally administered synthetic morphine-like drug, is easily used on an outpatient basis. Tramadol may have synergistic effects when coupled with an NSAID. Potential adverse effects of opiates include respiratory depression, sedation and constipation.
Coarse fraction radiotherapy plays a crucial role in the management of tumor-related pain. Candidates for palliative radiation include those with non-resectable osteosarcoma, bone metastases, and non-resectable soft tissue sarcomas and carcinomas. Treatments are scheduled once weekly for three to six treatments. Palliative radiation can be used in conjunction with other pain management strategies.
In the management of moderate to severe pain, especially when seen with bone tumors, the combination of an NSAID, tramadol and gabapentin (a calcium channel blocker used for neuropathic pain control) is a great combination to keep our patients comfortable. Breaking the pain cycle and preventing a ramp up of the pain receptors can provided improved quality of life if additional treatment is not an option for our patients. Please call us if you have any questions about cancer pain management. We would be happy to discuss your case with you.
In addition to medically managing pain, Dr. Bill Brewer would like to note that reduction of the tumor itself can significantly contribute to pain relief.
For questions about managing pain in your cancer patients, please call Dr. Bill Brewer at our Greenbrier hospital and Dr. Nicholas Rinaldi at our Town Center hospital.
Management of Unresectable Mast Cell Tumors in Dogs
Mast cell tumors are the most common skin tumors in dogs. Their biological behavior is variable; most of the tumors are easily treated with wide-margin surgical removal, but some are more aggressive and carry higher potential for local recurrence and distant spread to the lymphatic system and visceral organs (such as liver and spleen). Local treatment can sometimes be very challenging, especially in situations where the masses are large and locally infiltrative, located at extremities of the body or when there is evidence of tumor spread to local lymph nodes or distant locations. Various forms of treatment have been evaluated for unresectable MCT in dogs including oral prednisone, lomustine (CCNU), Leukeran®, hydroxyurea and intravenous vinblastine (VBL); however, response rates are relatively low (~50% and less), and responses are typically short-lived. The tyrosine kinase inhibitor (TKI), toceranib phosphate (Palladia™), has proven, single-agent activity against canine MCT, but tumor size reduction was found in less than half of the patients treated.
A recent article, “Pulse-Administered Toceranib Phosphate and Lomustine for Treatment of Unresectable Mast Cell Tumors in Dogs” (Burton J.H. et al., JVIM 2015; 29:1098-1104) evaluated a new approach for treatment of large mast cell tumors, where surgery was difficult to justify. The theory behind this study came from data supporting a synergistic effect for use of tyrosine kinase inhibitors (such as Palladia and sunitinib) in combination with chemotherapy and/or radiation therapy in different types of human and canine tumors. The combination of VBL and Palladia was already evaluated for dogs with MCT but significant dose reductions were needed in VBL dose due to severe bone marrow suppression. Chronic use of Palladia can also be problematic due to a wide range of complications (diarrhea, vomiting, lethargy, neutropenia, proteinuria and others).
The authors suggested that Palladia will sensitize tumor cells to chemotherapy and that low-frequency use will reduce its costs and side effects. This was a phase I/II, multicenter, prospective clinical trial that evaluated 41 dogs with measurable (>1cm) MCT confirmed by cytology or histology. The phase I CCNU dose-escalation portion of the study determined the maximum tolerated dose of Palladia. In phase II, Palladia was given only on days 1, 3 and 5 of a 21-day cycle, and CCNU was given on day 3 of each cycle. Most dogs treated were of middle to older age (median 8.2y), with a median weight of 28.2kg. Mixed breed and boxers were the most common breeds. The median tumor size was 6.7cm (range 0.84-21.8cm). Local lymph node and distant metastasis were found in 26 and 5 dogs, respectively. Side effects were mostly mild to moderate and included neutropenia (34 dogs), hepatotoxicity (24 dogs) and GI toxicity (vomiting, 15 dogs; diarrhea, 11 dogs). Overall, 16 dogs had CCNU dose reductions and/or treatment delays. The overall response rate was 46% (15 had partial remission, and 4 had complete remission). The median time to maximum response was 21 days, and median overall survival was 131 days. Dogs with tumors 6.7cm). Patients with no previous chemotherapy also had better MST at 146 days (vs. 50 days with previous treatment).
To summarize, pulse-dosed Palladia in combination with CCNU was well tolerated and caused less GI side effects than with standard frequency use of Palladia. The response rate here (46%) was comparable to other single-agent protocols but superior than reported in a recent multicenter study for use of CCNU as a single agent (23%). This protocol provides a good alternative for treatment of large mast cell tumors, and it may be more appealing to owners who decline parenteral chemotherapy treatment but cannot afford monotherapy with Palladia.
We would like to thank our colleague from BluePearl in Washington, Sharon Shor, DVM, MS, DACVIM-Oncology, for allowing us to use this article in Companion.
Feline Hemotropic Mycoplasmosis
Mycoplasma haemofelis organisms can be seen adhered to the cell membranes of affected red blood cells.
Based on gene sequencing, the species formerly classified as Hemobartonella felis has been subdivided into two groups, the larger Mycloplasma haemofelis and the smaller Candidatus Mycoplasma haemonitinutum. Mycoplasma haemofelis is more likely to cause clinical anemia than Candidatus Mycoplasma haemonitinutum; however, the latter is suspected to promote the ability of feline leukemia virus to induce cancer in co-infected cats. Fleas, and possibly other blood-sucking insects such as ticks, lice and mosquitoes – are responsible for transmission of the infection.
Identification of the organism on the periphery of red blood cells utilizing fresh blood smears, rather than smears done from EDTA or heparinized blood, remains the preferred diagnostic test. PCR testing is more sensitive than microscopic detection of the organism; however, it is more likely to detect asymptomatic carriers.
A three-week course of doxycycline is recommended to treat feline hemotropic mycoplasmosis. Enrofloxacin may also be effective and can be tried in those cats intolerant of doxycycline. Azithromycin has not been shown to work. Despite resolution of the anemia with treatment, many cats remain carriers of the disease. Newer medications are being evaluated with the goal of eliminating the carrier state.
Please call Dr. Leigh Perry with any questions, 757.499.5463.
WANTED: Cats with Chronic Kidney Disease for an Anemia Trial
BluePearl Veterinary Partners is currently recruiting patients for a fully-funded trial to evaluate the safety and efficacy of an oral medication to manage anemia associated with chronic kidney disease in cats. The study consists of two phases: the efficacy phase (28 days) and the maintenance phase (8 weeks).
- Cats, > 1 year old, male or female, > 2.0 kg
- Not pregnant, lactating or intended for breeding
- Diagnosis of chronic kidney disease
- Non-regenerative anemia with PCV < 27% at study days -7 and 0
- Stable concurrent medical conditions
- Cats may be receiving SQ fluids
- Fractious cats • Positive urine culture on study day -7
- Systolic blood pressure > 165 mmHg on study days -7 or 0
- Previous treatment with erythrocyte stimulating agents (ESA), including erythropoietin (EPO)
- Previous blood transfusion since being diagnosed with CKD
- Severe clinical signs of inflammation not attributed to CKD
- Other significant uncontrolled medical issues
- FeLV+ or FIV+ (if not vaccinated, sponsor will cover the cost to test)
- Obvious signs of GI bleeding
The study medication, diagnostic lab work and examinations will be provided at no cost to owners. Owners will be expected to administer the study medication at home, keep an owner diary and comply with study protocols.
*Note that this study is not funded for diagnostic or treatment costs associated with the underlying renal disease. Those costs must still be assumed by the owner.
For more information, or if you have a patient who may meet the above requirements, please contact Dr. Leigh Perry at our Virginia Beach Town Center hospital, 757.499.5463.
Meet Marlene Pariser, DVM, DACVD
Marlene Pariser, DVM, DACVD
Like many veterinarians, Dr. Marlene Pariser became a veterinarian because of her love for animals. Specializing in dermatology was almost a foregone conclusion because her father, uncle and grandfather were all MD dermatologists. She is especially interested in drug and clinical trials and the treatment of resistant infections. Married to another veterinarian, Dr. Pariser and her husband spend their free time on a farm in western Virginia.
What is the most interesting thing about you that only your closest friends or family members know about you?
I have really bad motion sickness. I am okay in cars but with any other form of travel, I must medicate myself and sit in only one position, or it’s really bad. I can’t even sit in rocking chairs anymore. I’ve been through all kinds of testing and physical therapy to improve my symptoms, which has helped. But I’m told they will never be totally resolved.
How do you unwind at the end of the day?
Spending time with my fur kids and husband. I am really a homebody!
What keeps you up at night?
Anxiety about difficult cases and how I can help my patients feel better
What would you be doing today if you could not have been a veterinarian?
I feel that I would still be doing something with animals, perhaps something involved with animal behavior or animal handler.
If someone wrote a biography about you, what do you think the title should be?
Crazy Blue Cat Lady
Outside of veterinary medicine, at what do you consider yourself to be an expert? A mess?
I am best at being a cat servant. As of right now there are three that totally run my life. We will have to see how well they share when their human brother is born. I am a total mess at doing things the easy way. The joke is there is the easy way, then there the way I am going to do it.
What is your favorite piece of technology?
My iPhone. I will have a panic attack if I don’t have my phone.
What’s on the horizon in dermatology that you are excited about?
Atopic dermatitis medications that are in the pipeline. Atopic dermatitis affects so many animals, and not all respond to all therapy. Having many options lets us best treat our patients who don’t respond to therapy or have special needs.
If you were given $10 million that you were required to give away, how would you spend it?
I would give it to well deserving organizations who use the money to help people/animals.
If you knew then what you know now, what would you do differently?
Nothing. I wouldn’t change anything! I am very happy with my life…well, maybe give up on some of the 90s fashion trends I fell for.
Other than a family member, who has made the biggest impact on your life so far?
The other residents who went through training with me. We have been through a lot during our training and have all supported each other.
What has made the biggest impact on who you are today?
My family. I grew up in a very strong family that always pushed education and science, which led to my current profession and specialty.