2016 SPRING: Pythiosis | Tickborne Diseases | Glaucoma | Electrochemotherapy | News From Our New Medical Director | Meet Dr. Cheryl Agent, Emergency Medicine
The Diagnostic Challenges of Fungal Disease: A Case Study
Jacqueline Nobles, DVM, DACVECC
Pythiosis is a pseudofungal disease of the gastrointestinal and integument systems. It is caused by an aquatic oomycete, Pythium insidiosum. The condition has been diagnosed in several species including humans, dogs, horses, cats, cattle and captive exotic species. Pythiosis is diagnosed most frequently in tropical and subtropical areas such as southeast Asia and the Gulf Coast region of the United States, but it has recently been reported in dogs as far west as California. Young animals, particularly large breed males with frequent access to warm freshwater habitats are usually affected. In dogs, infection usually results in either segmental gastrointestinal masses of the esophagus, stomach or colon. Additionally, it can manifest as ulcerative nodular skin lesions. While biopsies are definitive, an enzyme-linked immunosorbent assay (ELISA) is available through Auburn University. Unfortunately, in many cases the extent of the disease and lesion location often preclude complete surgical resection, and effective medical therapies are lacking. Thus, the prognosis for pythiosis in canines is poor with a reported median survival time of 26.5 days (JVIM2008).
I wanted to share with you a case of gastrointestinal pythiosis that we recently diagnosed in a 3-year-old, castrated male, lab mix. He presented to the BluePearl Oklahoma critical care and internal medicine services with a chief complaint of weight loss. According to the owner, the patient had lost about 20 pounds in the last 4-6 weeks. On abdominal palpation, a suspected mass was palpated in the cranial abdomen. An abdominal ultrasound showed marked thickening of the gastric wall (~1.5cm), thickening of the ileocecocolic junction, and mesenteric lymphadenopathy. Aspirates of the stomach wall showed predominately eosinophilic inflammation with fungal hyphae present. A serum ELISA for Pythium was submitted to Auburn University (Dr. Joseph Newton’s lab) and found to be positive. While I warned the owners of a poor prognosis, they wanted to pursue medical therapy. I have been treating him with prednisone, itraconazole and terbinafine. In one month, he has clinically responded very well as evidenced by weight gain and resolution of the anorexia. While I suspect his disease will return in the next 8-12 weeks, he is responding well to therapy at this time.
If you have any questions about this disease or suspect you may have a patient with pythiosis, please feel free to contact our criticalist, Dr. Jacqueline Nobles, 405.749.6989 or Jacqueline.email@example.com.
Canine Tickborne Diseases
Ticks are important parasites capable of transmitting a wide array of pathogens to our canine patients. They have been documented to harbor multiple pathogens instigating co-infections. Geographic distribution of tick-borne disease varies widely within the United States. Travel history and expansion in tick populations may introduce disease to new geographical areas.
Ticks are free-living arthropods that require blood meals during at least one life stage. A blood meal is initiated by piercing the host’s skin followed by the release of approximately 120 inflammatory and vasoactive chemicals. These chemicals help to sustain conditions for a successful meal and ensure the recruitment of inflammatory host cells and prevention of clotting.
There are two general categories of ticks. Soft ticks attach to the host, complete feeding within minutes, and then detach. The hard ticks are protracted feeders that remain attached for up to several days. Successive blood meals from different hosts allow for transmission of pathogens from host to host. Risk of disease transmission is a function of prevalence of infectious ticks and the likelihood of an encounter between infected tick and susceptible host.
The haemoplasma known to cause disease in dogs is M. haemocanis (formerly known as Haemobartonella canis). These organisms are small bacteria that reside on the surface of red blood cells (RBCs) and can induce hemolytic anemia in the host. Canine patients that contract this disease tend to have a history of splenectomy, are immunosuppressed, or have concurrent infections. The vector is the Rhipicephalus sanguineus tick. Clinical presentation depends upon acute versus chronic infection, and concurrent disease or infection. Clinical signs may include anemia as well as dehydration, anorexia, lethargy, weight loss, depression, and intermittent pyrexia. Diagnosis is made by performing a blood smear and visualizing the organisms on the surface of the RBCs or detecting DNA via polymerase chain reaction (PCR). Treatment recommendations include the use of tetracyclines or fluoroquinolones for three weeks. Although these antibiotics have been documented to treat clinical disease, their use does not always result in a negative PCR.
Borrelia burgdorferi (Lyme disease)
B. burgdorferi is a spirochete transmitted by the Ixodes scapularis (deer) and I. pacificus (Western black-legged) tick. Dogs seem to be primarily affected by the adult tick, which transmits the disease after approximately 24-48 hours of feeding. After transmission, the spirochetes disseminate and cause polyarthritis, fever, anorexia, and/or lymphadenopathy. Some cases will also develop a protein losing glomerulonephropathy (Lyme nephropathy). A pathognomonic test for Lyme disease does not exist. Diagnosis must be made on the combination of clinical signs, knowledge of disease distribution, travel history, and accurate diagnostic tests. The production of antibodies against the VlsE protein (a conserved region of B. burgdorferi) is documented to be associated almost exclusively with B. burgdorferi. The C6 ELISA (SNAP 4DX) utilizes the C6 peptide as the diagnostic antigen and detects infections with B. burgdorferi with high sensitivity and specificity. Vaccines do not induce the C6 antibody response and the C6 ELISA is therefore useful in distinguishing between vaccination and infection. Most exposed dogs (90-95%) do not develop clinical signs, and it is extremely important to discriminate between infected seropositive animals from those testing positive due to exposure. If clinical signs are going to appear, they usually do so weeks to months after exposure. The treatment of choice is doxycycline at 10mg/kg q12-24h for 30 days; however amoxicillin and other beta-lactam antibiotics may also be used.
Engorged dog (wood) tick
Anaplasma phagocytophilum (granulocytic anaplasmosis)
Anaplasma phagocytophilum are small, obligate, intracellular bacteria. These organisms reside in the granulocytic white blood cells, primarily the neutrophils (hence the name canine granulocytotropic anaplasmosis). Transmission is accomplished via the I. scapularis and I. pacificus and requires a minimum feeding time of 24 hours. Reported clinical signs are most often associated with acute disease. However, subclinical disease is also likely given the large number of dogs exposed, compared to the few numbers of clinically ill dogs in endemic areas. Clinical signs may be vague and include fever, lethargy, and anorexia. Less common presentations may also include polyarthritis, lameness, gastrointestinal disease, hepatosplenomegaly, central nervous system signs, lymphadenopathy, and respiratory disease. Diagnosis is achieved by identification of morulae in the white blood cells, ELISA (SNAP 4Dx Plus), serology, four-fold rise in antibody titers, Western blot, and/or PCR. Doxycycline at 10mg/kg/day for 3 weeks is the treatment of choice.
E. canis is the causative agent of canine monocytic ehrlichiosis. The vectors responsible are the R. sanguineus and Dermacentor variabilis ticks. Infections can be acute, subclinical or chronic and can cause multisystemic symptoms. Clinical signs are vague and patients may present with fever, myalgia, depression, pale mucous membranes, weight loss, reduced white blood cells, reduced platelets, hepatosplenomegaly, edema of extremities, anterior uveitis, epistaxis, retinal hemorrhages, and/or neurologic signs. Another consequence of this disease may be renal failure instigated by vasculitis. Identification of morulae, serology, four-fold rise in antibody titers, Western blot, and/or PCR is needed for diagnosis. Doxycycline at 10mg/kg/day for 3-4 weeks is the recommended treatment. Vaccines are not currently available. Tick control measures are the staple of prevention.
Rocky Mountain spotted fever (RMSF)
Engorged deer tick
Rickettsia rickettsii is an obligate intracellular gram-negative bacterium and is the causative agent for RMSF. The ticks associated with this disease are D. variabilis (American dog tick) and D. andersoni (Rocky Mountain wood tick). A latent period of 5-20 hours of tick feeding is needed for transmission. Fever, lethargy, vomiting, anorexia, petechiae/ecchymoses, ocular lesions, joint pain, and neurologic signs may be exhibited by infected dogs. If treated early or mildly affected, dogs may make a rapid and complete recovery. However, permanent organ damage (especially organs within the cardiovascular, neurologic, and renal systems) may result in those severely affected. Diagnosis is based on documentation of a four-fold rise in serum antibody titer. Treatment recommendation is the administration of doxycycline at 10mg/kg/day for 7 days.
B. vinsonii, subsp. berkhoffii, is a small, fastidious, gram-negative bacterium. Demonstrated transmission via Ixodes species and R. sanguineus has been documented but other arthropods have been implicated (flea, biting flies, keds, lice, sand flies). Clinical signs can range from a mild transient fever to endocarditis, cardiac arrhythmias, intermittent lameness, bone pain, ocular disease, meningoencephalitis, anemia, thrombocytopenia, and epistaxis. Bartonella primarily affects the aortic valve and causes lesions characterized by fibrosis, mineralization, endothelial proliferation, and neovascularization in cases of infectious endocarditis. Diagnosis is based on culture and serologic testing with PCR being potentially more sensitive. No regimen of antibiotic treatment has been proven to be effective in controlled studies with long term follow up. Current recommendations include treatment with enrofloxacin, doxycycline or azithromycin for 4-6 weeks.
To identify an engorged tick, inspect the legs and the upper part of the body.
Classification of Glaucoma
Glaucoma is an increase in the intraocular pressure (IOP) to a level that is incompatible with the health of the eye, and it is the single most common cause of blindness in dogs. It is always the result of a decrease in aqueous humor outflow, never the result of an increase in aqueous humor production. Aqueous humor is formed by the ciliary body then flows between the lens and iris into the anterior chamber where it drains into the iridocorneal angle (ICA).
The clinical presentation of glaucoma is a globe with marked scleral injection, corneal edema and a mydriatic pupil +/-vision.
Marked scleral injection, corneal edema and vascularization consistent with glaucoma.
Anterior lens luxation with the lens in the anterior chamber
Anterior uveitis results in pooling of inflammatory cells (hypopyon) in the ventral anterior chamber
Uveal neoplasm with severe inflammation blocks the ICA.
Hyphema filling the anterior chamber.
Anterior uveal melanosis in a Cairn terrier with pigment extending into the sclera.
Glaucoma can be classified in terms of the underlying cause.
In primary glaucoma there is no other recognized ocular disease process with a defect in the ICA or trabecular meshwork causing blockage in aqueous humor outflow. In these cases invariably the fellow eye will be affected despite prophylactic therapy. A number of breeds have been demonstrated to have a predisposition for the development of primary glaucoma.
Closed angle glaucoma, or goniodygenesis
In this case there is an abnormality, an extension of Descement’s membrane that spans the ICA preventing aqueous humor drainage. The onset of glaucoma in these cases is often acute and presents in middle age. Numerous breeds have been described as having a high predilection for closed angle glaucoma:
- English cocker spaniels
- American cocker spaniels
- English springer spaniel
- Basset hound
- Bouvier des Flandres
- Labrador retriever
- Great Dane
- Siberian husky
- Shih tzu
It is imperative that when these breeds present with a “red eye,” IOPs are checked and the fellow eye is treated prophylactically.
Primary open angle glaucoma (POAG)
In these cases the ICA is open. It is thought that glaucoma develops due to a build up of glycosaminoglycan in the trabecular meshwork that is upstream form the ICA blocking outflow. Another theory came from a study in Siamese cats with POAG, which described a degeneration of the sclera vessels where the aqueous humor ultimately drains from the eye. The exact mechanism of how aqueous drainage is prevented is unknown. In comparison to closed angle glaucoma less breeds have a predisposition to POAG; there are only three: Norwegian elkhound, beagle and shiba inu.
This is the most common glaucoma in both dogs and cats. It develops when ocular pathology blocks the ICA preventing aqueous drainage. The following are a list of common pathologies that result in secondary glaucoma.
Lens luxation is commonly seen in terrier breeds but has also been described in the shar pei and Chihuahuas. The lens may luxate into the anterior chamber carrying vitreous humor with it.
The vitreous overlaying the entrance to the drainage angle as well as the lens occupying most of the anterior chamber results in decreased drainage. Furthermore, the presence of vitreous or the lens in the pupil will impede aqueous from entering the anterior chamber (pupillary block). In some cases it is difficult to decide whether the lens luxation is a cause or an effect of glaucoma because buphthalmos is a sequelae of glaucoma that results in tearing of the lens zones then lens luxation.
Inflammation of the uveal tract, uveitis, results in blockage of the ICA through a variety of mechanisms:
- Accumulation of inflammatory debris in the ICA
- Swelling or damage to the drainage mechanism due to the inflammation
- The development of adhesions between the iris and lens (posterior synechiae resulting in the buildup of aqueous behind the iris displacing the iris forward (iris bombe)
- Fibro vascular membrane formation over the ICA
- A syndrome of uveitis with cysts has been described in golden retrievers, with the cysts resulting in glaucoma.
induces glaucoma by direct involvement of the ICA or a build up of neoplastic cells from the aqueous within the ICA. The most common intraocular neoplasms that affect the uvea are uveal melanoma, ciliary body adenoma/ adenocarcinoma and lymphoma.
The presence of blood (hyphema) and fibrin clots in the anterior may compromise aqueous flow. If the etiology of the hyphema is trauma, this may also result in ciliary body damage.
This is a condition that affects Cairn terriers; it involves the accumulation of pigment in the anterior segment instructions and the drainage angle. Large quantities of pigment are visible in the anterior chamber and the sclera
Determination of the underlying cause of glaucoma will influence which medical therapy is selected.
If you would like a consultation with our veterinary board certified ophthalmologists, please don’t hesitate to contact Dr. Kevin Donnelly, firstname.lastname@example.org, or Dr. Jeff Studer, email@example.com or at 405.749.6989.
We thank our colleague from BluePearl Veterinary Partners in New York, Patricia Mundy, VetMB, MRCVS, MA, DACVO, for allowing us to use this article for Companion and our colleague from The Animal Eye Institute, D.J. Haeussler, Jr., MS, DVM, DACVO, for allowing us to use his photographs.
Traditional chemotherapy is generally ineffective in treating measureable tumors. The objective response rate of most macroscopic and incompletely resected solid tumors to traditional injectable chemotherapy is often only 10-30% depending on the tumor type. The main reason for the lack of response is that it is difficult to achieve and maintain a prolonged concentration of chemotherapy within a tumor. The lipid bilayer of the cell membrane acts as a barrier to many chemotherapy drugs resulting in poor uptake into the cancer cell. Combining electrochemotherapy with traditional chemotherapy gives us hope that we will be able to help more pets beat cancer.
With electrochemotherapy, specific, short electrical pulses are delivered across the tumor of an anesthetized patient in a grid pattern either when the chemotherapy drug is at a maximum concentration in the blood or after chemotherapy is injected into the tumor directly. The pulses create pores within the cell membrane, and chemotherapy is able to move intracellularly. This allows a much higher concentration of chemotherapy to be administered to the tumor while sparing normal tissues in the area.
Treatments are generally spaced apart by 2 weeks, and as many as 6-8 treatments can be performed as long as the tumor is responding.
Electrochemotherapy has been demonstrated to be effective against squamous cell carcinoma and other carcinomas on external surfaces of the body, mast cell tumors, mammary tumors, perianal tumors, papillomas and soft tissue sarcomas. When a tumor can be removed with complete surgical margins, this is still the standard of care, but if a tumor is in an area where complete margins cannot be obtained, electrochemotherapy can be considered.
Generally well-tolerated, systemic side effects such as nausea, vomiting, diarrhea or bone marrow suppression are uncommon with this modality, but we generally recommend a complete blood count be performed 1 week after treatment. Local side effects may include inflammation and redness of the skin or mucous membranes in the area being treated. Anti-inflammatory medications can be utilized in appropriate patients.
The oncology service at BluePearl in Oklahoma now offers electrochemotherapy. For more information contact Lindsay Donnelly, DVM, MS, DACVIM-Oncology, firstname.lastname@example.org or 405.749.6989.
FROM THE MEDICAL DIRECTOR
Medical Director’s Column
I hope you enjoyed our mild winter and are looking forward to spring, which in Oklahoma is always exciting and one of my favorite times of year. This spring looks to be very exciting for our veterinary community.
I have recently accepted the role of Medical Director of BluePearl in Oklahoma. Through my first months here, I have enjoyed getting to know many of you and working together with you to provide excellent care for your patients and clients. This position will allow me to get to know you even better. I will continue to see ophthalmology cases on a daily basis. If there is anything I can do to improve our relationship with you, your patients or your clients please do not hesitate to contact me.
We are thrilled to introduce you to the BluePearl Portal. This is an exciting tool that has been developed as a commitment to exceptional communication with you. It will not replace timely personal communication with you, but it will allow you 24/7 password-protected access via our website to medical records of your patients that have been seen at BluePearl. We expect the Portal to enhance your experience with us. You should have access to the Portal now and be getting notifications and records through it. If you have any questions, contact our veterinary relations coordinator, Joy Hardin, at 405.749.6989 or email@example.com.
We are also excited about our move to a new hospital at the end of this year. We officially broke ground on March 1, and construction is proceeding nicely. It will be located on Memorial Road (next to Main Event) across from our current location. This 18,500 square foot, state-of-the-art hospital will allow us to all be under one roof to better serve you and your pet families. We will keep you updated as we move forward.
One of our favorite parts of partnering with you is providing state board-approved CE. We offer subjects (and free food) that we hope are interesting to both you and your team. We invite you to join us for one of our upcoming CE events. Please check our online calendar regularly for the most current information about courses, dates and locations.
The future is bright in Oklahoma City! I am excited about continuing to partner with you as we all strive to enrich lives through remarkable care for the pets of Oklahoma.
Jeff Studer, DVM, DACVO
FROM THE MEDICAL DIRECTOR
Meet Dr. Cheryl Agent
Emergency Medicine Service
Dr. Cheryl Agent, Emergency Medicine Service
Dr. Agent had the privilege to work with a veterinarian many years ago and was enthralled, enamored and fascinated by the medicine and the work. Interested in pursuing the same path, she determined that veterinary school wasn’t feasible at the time because she had two small children. But as life would have it when you cherish a dream, the opportunity finally came along, and she eagerly went back to school. Upon graduation, Dr. Agent immediately stepped into the field of emergency medicine and has been there ever since.
How do you collaborate with the primary care veterinarian?
I believe it is essential to keep the primary care veterinarian updated. I use personal phone calls, emails and faxes to keep them current on the case and work with them to develop treatment plans and make medical decisions. I think it is important to respect the established relationship they have with their client.
How do you go about helping ease the concerns of an upset client?
I feel it is important to quickly build a rapport with clients. I actively listen to their concerns and make it very clear that my number one concern is the comfort and well-being of their pet. I make every effort to give them all of the information they need and make them feel comfortable with the decisions that they are making. In emergency medicine, we are often handling unexpected, tough cases with upset owners, and it’s important to put ourselves in their shoes and empathize with their situation.
What keeps you interested in cases day-after-day?
The constant variation, continued learning and challenges of emergency medicine keep me interested. I also love watching the interaction between the pet and owner when a patient who was very ill is released to go home, happy and healthy again.