Inflammatory disease is the second most common cause of hepatobiliary disease in cats.  The histological classification of feline inflammatory liver disease is confusing. Terms used in the literature have included suppurative or acute cholangiohepatitis, chronic cholangiohepatitis, chronic lympocytic cholangitis, progressive lymphocytic cholangitis, sclerosing cholangitis, lymphoplasmacytic cholangitis/cholangiohepatitis, lymphocytic portal hepatitis, and biliary cirrhosis.  This lack of consistency has made it difficult to compare reported cases.  In 2004 the WSAVA Liver Disease and Pathology Standardization Research Group proposed a new classification scheme in order to provide consistency in terminology. Since the group felt that the inflammation was primarily centered on the biliary tree it defined 3 distinct histopathologic forms of feline cholangitis; 1.) neutrophilic cholangitis (acute and chronic), 2.) lymphocytic cholangitis and 3.) chronic cholangitis associated with biliary fluke infestation.  Cats can get a true chronic hepatitis but it is rare.  Copper toxicity would be one rule out.

Acute neutrophilic cholangitis (ANC) is marked by accumulationof neutrophils in the lumen and/or epithelium of the bile ducts with associated bile duct degeneration and necrosis. Edema and PMN’s may break through the limiting plate leading to cholangiohepatitis.  Cat presenting with ANC are typically younger (<5 yrs old) than cats with other forms of cholangitis Typically they have an acute onset of lethargy, anorexia, vomiting, +/-  icterus, fever and abdominal pain.  They may have a leukocytosis on CBC with a left shift or toxic changes and  mild to moderate increases in ALT and GGT. ALP may be normal or mildly elevated.  On diagnostic imaging choleliths, thickened GB or biliary duct walls may be present (Fig 1).  ANC is almost always associated with bacterial infection.  Culture of the liver or preferably bile should be part of the work-up. Enteric aerobic and anaerobic organisms are isolated.  E coli is the most common isolate. Most cats will have some pre-disposing cause for biliary tract infection (e.g. choleliths, inflammatory bowel  disease, infectious nidus elsewhere in the body or concurrent chronic cholangitis). Treatment is with antibiotics for 6-8 weeks +/- hepatoprotectants and choleretics.

Chronic neutrophilic cholangitis (CNC) is marked by a mixed inflammatory infiltrate (neutrophils, lymphocytes and plasma cells) in the bile ducts and periportal area with associated bile duct proliferation and varying degrees of peri-portal fibrosis which can bridge portal areas.  Concurrent IBD (83%) and/or pancreatitis (50%) can occur. The clinical presentation is typically a middle aged to older cat with a history of waxing and waning signs of vomiting and intermittent anorexia. Weight loss may be present.  On physical examination the cats may have hepatomegaly and icterus. Typically all serum liver enzymes are increased. Some cats may have hyperglobulinemia.  Ultrasound of the liver may be normal or may show hepatomegaly. The liver may be hyperechoic or hypoechoic with prominent markings. US changes in the gallbladder and biliary ducts (wall thickening, mineralization, presence of biliary sludge) may be present.  Concurrent changes in the pancreas and intestinal tract consistent with chronic inflammatory disease may be seen. Some cats present for bile duct obstruction from choleliths or inspissated bile.  Many cats have evidence of secondary bacterial infection, and culture of a liver biopsy or bile aspirate should be done. Etiology of this disorder is unknown. It may be immune in origin or possibly a reaction to the presence of chronic bacterial infection or chronic exposure to bacterial products.  Treatment usually consists of hepatoprotective agents (SAMe, ursodeoxycholate, vitamin E, silymarin) and a 6 week course of antibiotics.  After antibiotic therapy many cats are tried on an immunosuppressive course of prednisolone.  Therapy should be directed at concurrent IBD if it is suspected.  Hypoallergenic or novel ingredient diets along with parenteral supplementation with vitamin B12 is in order.

Lymphocytic cholangitis is marked by infiltration of small lymphocytes in the portal areas with lymphocytes centered around bile ducts or present in the biliary epithelium. Variable degrees of portal fibrosis and bile duct proliferation are present. There may be rare plasma cells and eosinophils.  Based on H&E staining alone it may be very difficult to distinguish lymphocytic cholangitis from a small cell lymphoma.   Ductopenia, peribiliary fibrosis, immunologic targeting of the bile ducts and lipogranulomas were more common with lymphocytic cholangitis than with small cell lymphoma.  Immunophenotyping may be of some value in making the determination as most (but not all) cases of lymphocytic cholangitis are a mixture of B and T cells (often portal aggregates of B cells are present,  while small cell lymphomas are either exclusively B or T cells). Tests for clonality can be done on biopsy material as well with most lymphomas being derived from one clone.  Clinical presentation in cats with lymphocytic cholangitis is similar to that seen with CNC but these cats often have an even more insidious onset.  Therapy for lymphocytic cholangitis is a combination of prednisolone with chlorambucil +/- vitamin B12 supplementation and hepatoprotectants.

Chronic cholangitis associated with biliary fluke infestation is characterized by dilated large bile ducts with papillary projections and associated marked periductal and periportal fibrosis. There are scant to moderate mixed inflammatory cell infiltrates within the bile ducts or periportal areas. There may or may not be eosinophils present. Treatment is with praziquantel. The intermediate hosts for the flukes are not present in New England.

It should be noted that some old cats get a progressive accumulation of lymphocytes in the portal regions of the liver.  This appears to be reactive lesion and may not be associated with primary hepatobiliary disease. It has been called lymphocytic portal hepatitis in the literature.  Over 80% of cats greater than 10 years of age have this lesion.

Labrador retrievers develop a breed-specific chronic hepatitis (CH) that progresses to cirrhosis and hepatic failure. Vague clinical signs include decreased appetite, lethargy, PU/PD and vomiting.  Median age at diagnosis is between 6.4-9.3 years (range: 2-15 years).   A female predominance is noted in some, but not all reports.  Dogs typically have increases in serum  ALT and AST with more modest and variable increases in ALP and GGT. Some dogs also have renal tubular disease manifested by the presence of normoglycemic glucosuria.  Definitive diagnosis is by hepatic histopathology, which shows varying degrees of necrosis/apoptosis with centrolobular to periportal mononuclear inflammation (lymphocytes, plasma cells and histiocytes), regeneration and fibrosis (Fig 3). In some dogs cirrhosis is present at diagnosis.   Median survival is 374 days (range,1-2,645 days).

Figure 3: Hepatic biospy from a 5 year old spayed female Labrador that presented for anorexia, weight loss, and PU/PD. H and E stains (A, B) show marked portal inflammation consisting of lymphocytes, plasma cells and macrophages. Multifocal lipogranuloma’s are present. Siruis Red stains (C, D) highlight the abundant fibrosis with prominent bridging between portal areas. Low (A C, 100X)) and high (B, D 400X) power.

The etiologic factors in Labrador CH have not been fully characterized. Some dogs accumulate excess hepatic copper, but it is unknown if this copper accumulation is the primary cause for the inflammatory process or simply predisposes the liver to harm from other insults such as toxic or immune injury.  Without identification of a specific etiologic trigger, no standard treatment for Labrador CH exists. Copper chelation therapy, low copper diets and a variety of hepatoprotective agents (vitamin E, ursodeoxycholate and S-adenosylmethionine) are recommended, although these have not been shown to stop disease progression.  Anecdotal evidence suggests that some dogs respond to immunosuppressive therapy with prednisone. Prednisone therapy, however, can be associated with serious side effects in dogs with compromised hepatic function, including worsening of ascites and hepatic encephalopathy, gastric ulceration, and increased susceptibility to portal vein thrombosis. Thus alternative therapies to capture remission are necessary.

At Tufts we are beginning an innovative pilot study to look at the therapeutic efficiency of mesenchymal stem cells in treating canine CH.  Human clinical trials using MSCs to treat CH have demonstrated decreases in serum liver enzyme activity and/or improvements in clinical or hepatic histological scoring systems. Of particular interest is the fact that MSC therapy can ameliorate hepatic fibrosis.   The effect of MSCs may be due to their ability to differentiate into hepatocytes in vivo and thus aid in hepatic regeneration, and/or to the presence of paracrine effects which suppress inflammation and collagen deposition.  Inclusion criteria for the Labrador study include the presence of moderate to severe activity on hepatic biopsy and a serum ALT and/or AST at least 3 times the upper limit of normal.  Contact Dr. Cynthia Webster (cynthia.leveille-webster@tufts.edu) or our clinical trials technician, Jessica Schavone (jessica.schavone @tufts.edu) if you have interested clients.  Funds are available to off-set the cost of the medical work-up (including laparoscopic hepatic biopsy) and all treatments are free. 

Fig 2. Hepatocutaneous syndrome in a dog. A. Gross appearance of feet with hyperkeratosis and ulceration. B. Ultrasound of liver showing typical ‘honeycomb’ pattern consisting of variable-sized hypoechoic regions surrounded by hyperechoic borders. B. Skin biopsy (H&E) with 1: Marked parakeratotic hyperkeratosis; 2: Vacuolar change in the upper levels of the epidermis; 3. Hyperplastic epidermis with acanthosis Images A and C courtesy of Dr Lluis Ferrer and B from Dr. Dominique Penninck.

The scrotum was similarly involved. The finding of these skin lesions along with the increased liver enzymes without signs of hepatic functional failure (normal albumin and bilirubin, PT, PTT) suggested the possibility that the skin lesion may at this time be something different than a simple bacterial pododermatitis, and Dr. Lluis Ferrer, our dermatologist, agreed. Both of us suspected hepatocutaneous syndrome (HCS). Ultrasound of the liver provided additional evidence to support our presumptive diagnosis, as the liver had the ‘honeycomb’ pattern consisting of variable-sized hypoechoic regions surrounded by hyperechoic borders typically seen with HCS (Fig 2B).  The histopathological correlate to this US appearance is the presence of multiple small, regenerative type nodules with fat/glycogen accumulation organized around fibrous bands of tissue with areas of parenchymal collapse. In order to obtain a definitive diagnosis of HCS we obtained a skin biopsy and a plasma amino acid profile (UC Davis). The owner was reluctant to pursue a laparascopic liver biopsy at this time.  Skin scrapes and scotch tape preparations of the skin were negative for Demodex and Malassezia. The skin biopsies showed the typical histopathologic changes consisting of marked parakeratotic epidermis with striking inter- and intracellular edema from necrolysis in the upper epidermis, and hyperplastic basal cells, creating the “red, white and blue” lesion that is diagnostic for this disease (Fig 2C). The amino acid profile showed severe hypoaminoacidemia. The dog was treated with intravenous infusions of amino acid every 3 weeks for 6 months, and switched to a high quality protein diet supplemented with an amino acid powder.   Secondary infection was controlled with topical washes and antibiotic therapy for 8 weeks. The dog has done extremely well and is alive and asymptomatic 2 years after diagnosis. He is being maintained on diet and oral AA supplements along with anti-oxidants (vitamin E) and hepatoprotectants (s-adenosylmethionine).  Serum liver enzymes are mild to moderately elevated but hepatic function tests (albumin and bilirubin) are normal.  Unlike many dogs with HCS that can be controlled, this dog has not gone on to develop diabetes mellitus.

In order to be a good hepatologist, I rely heavily on a talented team of professionals at Tufts. Many small animals with hepatobiliary disease present with nonspecific signs and evaluation of clinical pathology seldom provides precise diagnostic clues. Diagnosis is complicated by the liver’s wide-ranging role in digestion, intermediary metabolism and biotransformation that makes it sensitive to secondary injury from many systemic disorders. As the liver diseases discussed in this issue of Progress Notes illustrate, the diagnosis of hepatobiliary disease often requires expert diagnostic imaging (ultrasound and scintigraphy) as well as histopathologic interpretation of hepatic biopsy material.  We are fortunate at Tufts to have one of the pioneers in hepatobiliary ultrasound, Dr Dominique Penninck, as well as pathologists with a strong interest in the liver including Dr Sam Jennings, who trained with the world renowned veterinary hepatic pathologist, Dr John Cullen, and Dr. Arlin Rogers, who has a career-long interest in animal models of hepatic cancer.  Both of our soft tissue surgeons, Dr. Ray Kudej and Dr. John Berg, have an interest in and aptitude for hepatobiliary and portovascular surgery and our cardiologist, Dr John Rush, is available to manage intrahepatic shunts with interventional radiology.  These individuals are complimented by a skilled group of board certified anesthesiologists who help us with the often complicated management of critically ill our patients with hepatobiliary disease. Lastly, we have a team of nutritionists, including Dr Lisa Freeman and Dr Calin Heinze, who help us meet the dietary requirement of our patients – in which nutrients of concern can include sodium, copper and/or protein balance. In addition, many hepatobiliary patients have a need for the placement of enteral nutrition tubes and occasionally formulation of balanced homemade diets.

Cynthia RL Webster, DVM, DACVIM (Small Animal Internal Medicine)
Professor, Associate Chair
DACVIM (Internal Medicine)
Post-Doctorate, Tufts Medical School, Department Physiology 1991-1993
DVM – Cornell University – 1985
BS – Simmons College – 1978

Dominique Penninck, DVM, ACVR
Professor
PhD – University of Liege, Belgium
DVM – University of Liege, Belgium
Diplomate, American College of Veterinary Radiology
Diplomate European College of Veterinary Diagnostic Imaging

Sam Jennings, DVM, ACVP
Assistant Professor
DVM – Tufts University Cummings School of Veterinary Medicine
MSpVM – North Carolina State University
American College of Veterinary Pathologists (Anatomic Pathology)

Arlen Rogers, DVM, Ph D, ACVP

John Berg, DVM, ACVS
Professor
Soft Tissue Surgery
MS – Colorado State University
DVM – Colorado State University
Board certification: ACVS

Ray Kudej, DVM, ACVS
Associate Professor
Soft Tissue Surgery
Post-Doctorate – Harvard Medical School
PhD – Iowa State University
DVM – Iowa State University
Board certification: ACVS

Lisa Freeman
Nutrition
PhD – Tufts University School of Nutrition
DVM with thesis – Tufts University School of Veterinary Medicine
BS – Tufts University
Board Certification:  American College of Veterinary Nutrition

Calin Heinze
Nutrition
Assistant Professor, Nutrition
MS – Nutritional Biology – University of California, Davis
VMD – University of Pennsylvania School of Veterinary Medicine
Board Certification: American College of Veterinary Nutrition (ACVN)

Lluis Ferrer, DVM, DACVD, PhD
Dermatology

John Rush
Interventional Radiology (IH Shunts)
Professor
Cardiology
DVM – Ohio State University
MS – Ohio State University
Board Certification Cardiology (ACVIM) and (ACVECC)

The Internal Medicine Service at Tufts Foster Hospital for Small Animals is led by faculty who are board-certified by the American College of Veterinary Internal Medicine. Supporting them are trained technicians(many who are also board certified by the National Association of Veterinary Technicians in America), as well as interns, residents, students and staff, within a state-of-the-art facility for providing diagnosis and advanced patient care.

The service handles a variety of clinical cases. Dog and cat patients—approximately 95% of the caseload—range from beloved pets to working dogs, from newborn kittens and puppies to geriatric cats and dogs. Tufts’ clinicians treat problems of the internal organ systems, including respiratory,neurological, gastrointestinal ,renal, infectious diseases and other conditions that need medical attention.

The service can provide intensive care for around-the-clock observation and treatment of critical patients. Some of the special procedures that can be performed include dialysis for acute kidney injury, laser lithotripsy for bladder stones, collagen injections for urinary incontinence, coil placement for liver shunts, gastrointestinal endoscopy, dietary consultation and obesity management, bronchoscopy and pulmonary function testing, rhinoscopy, and interventional procedures such as stent placement for collapsing trachea or nasopharygeal stenosis.

The enodurology team consists of:

Mary Labato, DVM

Linda Ross, DVM

John Berg, DVM

Robert McCarthy, DVM

Michael Goodrow, CVT

Small Animal Medicine Residents
Jessie Markovich, DVM
Faith Buckley, DVM
Samuel Tucker, VMD
Brandi Gallagher, DVM
Kelly O’Neill, DVM
Gideon Daniel, DVM
Daniel Jardes, DVM

Solitaire had been living with her breeder since approximately 4 weeks of age and her breeder recognized that the pup was always “wet” along her back legs and perivulvar region.  Solitaire appears to be continuously dribbling urine, however she does urinate voluntarily as well. The breeder felt that the pup did not seem to be bothered by the incontinence. She was concerned about the strong “urine odor” and the risk of urine scald. Solitaire was seen by her referring veterinarian who suspected an ectopic ureter. She was treated with a 10 day course of Clavamox for a suspected urinary tract infection. She was also treated with a 7 day trial of phenylpropanolamine to treat urethral sphincter mechanism incompetence which did not seem to help with the incontinence. The degree of incontinence prevented Solitaire to be an acceptable indoor companion.

On presentation to Tufts Foster Hospital for Small Animals, Solitaire was bright, alert and responsive with an ideal body condition score of 6/9. Physical examination was otherwise unremarkable except for urine staining along both rear limbs and a strong  odor of malodorous urine. There was mild urine scalding around the perivuvlar area. Otherwise, she was a happy “normal” puppy.

The differential diagnosis included ectopic ureter(s), ureterocele, pelvic bladder with urethral dysplasia and urethral sphincter mechanism incompetence. The initial workup included a complete blood count, serum chemistry profile, urinalysis and culture. The complete blood count revealed a neutrophilic leukocytosis, but was otherwise unremarkable. The chemistry profile was within normal limits. The urinalysis revealed concentrated urine with a relatively unremarkable sediment. Urine culture revealed a Proteus mirabilis urinary tract infection with sensitivity to multiple antibiotics.

An abdominal ultrasound was performed and revealed left hydronephrosis and hydroureter extending to the level of the urinary bladder. There was a question as to whether a ureterocele was present as well.

Solitaire was scheduled for cystoscopy and possible laser ablation of ectopia.  Cystoscopy revealed bilateral ectopic ureters. The right ureter was found to open in the distal urethra. This tunneling ureter was ablated using a Holmium YAG laser to the level of the trigone. The left ureter was ectopic as well and opened more distally in the urethra at the level of the external papilla. This ureter was ablated proximally to the level of the trigone. It was extremely dilated at the level of the bladder.  A neoureterosotmy was performed at the time of ovariohysterectomy. Urine was visualized empyting into the bladder from both ureters.

Solitaire recovered uneventfully from the procedure and immediately following post-operation the incontinence was minimal. She was discharged on Amoxicillin potassium clavulanate to treat the urinary tract infection and also given meloxicam as an anti-inflammatory agent post procedure. Future treatment options such as phenylpropanolamine or placement of a urethral occlusion device were discussed with the new foster owner.

Solitaire was completely continent for 5 days after the procedure and then incontinence returned when she was asleep or excited, but was much improved from her initial presentation. She was then prescribed 1mg/kg phenylpropanolamine every 12 hrs.

MaryAnna Labato, DVM, DACVIM (SAIM)

Endourology is the branch of urologic surgery concerned with closed procedures for visualizing or manipulating the urinary tract. The techniques are typically reserved for disorders of the urethra, urinary bladder, ureters and the pelvis of the kidney. In human medicine endourology has advanced tremendously over the past 20-30 years; however, in veterinary medicine the discipline is just starting to develop.

Some of the more commonly performed procedures in veterinary medicine include urethral stenting for the treatment of neoplasia and strictures, nephrostomy tube placement, ureteral stenting, percutaneous nephrolithotomy and cystoscopic–guided laser ablation of ectopic ureters and urethral transitional cell carcinomas. Additionally, lasers and shock wave lithotripsy may be used for the treatment of upper and lower urinary tract calculi.

 EQUIPMENT 

Various flexible and rigid endoscopes are used for traditional endourologic procedures.  Rigid cystoscopy is commonly performed in female dogs and cats for urethral and bladder access.  It is also possible in some animals to approach the ureters in this manner. Flexible ureteroscopes are used for urethral and bladder access in male dogs and for ureteral access in animals of acceptable sizes ( >15-20 kg). Rigid nephroscopes are used for percutaneous procedures of the kidney. Intracorporeal lithotripters (ultrasonic, pneumatic and electrohydraulic types) and the holmium:YAG laser are available for these procedures. The diode laser is used for endoscopic tissue resection, allowing for effective tissue cutting and tissue coagulation with limited bleeding. Extracorporeal shock-wave lithotripsy (ESWL) also has great application for small to moderate size nephroliths and ureteroliths.

Stents are commonly used in the urinary tract to treat obstructions in the urethra or ureter. A urethrane soft double pigtail ureteral catheter is the classic indwelling ureteral stent. A NITINOL ( Nickel and Titanium alloy from the Naval Ordinance Laboratory) self expanding metallic stent  (SEMS) is used for urethral obstructions.

For many of the more commonly performed procedures it is useful to have available either a C-arm fluoroscopy unit or an ultrasound machine to assist with guidance of the instruments and catheters. The C-arm Fluoroscopy unit is portable and permits various tangential views without moving the patient. Ultrasonography is useful for percutaneous nephrostomy and cystostomy tube placement. Guidewires and catheters of an assortment of sizes and shapes are needed for each procedure.

PROCEDURES

Urinary Bladder and Urethra

Laser Lithotripsy is a technique involving the intracorporal fragmentation of uroliths.  The laser tip is guided through the working channel of small diameter rigid or flexible cystoscope or ureteroscope. As the tip is advanced to within 5 mm of the urolith, the vapor bubble comes in contact with and impacts the stone. The stone is fragmented until the pieces are small enough to be removed normograde through the urethral orifice either via voiding uropropulsion or a stone basket. This process is useful for renal, ureteral, cystic and urethral uroliths; however, it is easiest to perform for urethral and cystic calculi. All stone types can be fragmented using laser lithotripsy. Laser lithotripsy should not be performed on male dogs < 7 kg or male dogs with large numbers of bladder stones.  In those cases, laparascopic-assisted lithotripsy is a more appropriate minimally invasive procedure.  Lithotripsy is a reasonable alternative to surgery in female dogs, female cats and male dogs with urethral stones. It is important to inform owners that urethral calculi in the male dog may end up in the bladder, requiring cystotomy, as dislodgement and retrograde movement of the urolith is a possibility. Cystoscopic stone basketing, (when a small basket device passes through the cystoscope that we use to scoop up the stone that we visualize and then remove it in the carrying basket that we have scooped it into) is an alternative if the stones or stone fragments are small enough to pass through the dilated urethra.

Antegrade Urethral Catheterization 

Urethral catheterization is typically a fairly simple procedure that is routinely performed for patients for whom attempts at routine retrograde catheterization have failed. It is important to note  there are circumstances when this techique may become problematic such as with very small female patients or patients with a urethral mass or a urethral tear.  In these cases, the technique can be performed under direct fluoroscopic visualization.

Urethral Stenting for Obstruction

Over 80% of animals with transitional cell carcinoma or prostatic adenocarcinoma experience dysuria, and approximately 10-30% develop complete urethral obstruction.  Chemotherapy, radiation therapy and laser ablation may be successful in shrinking the mass or slowing its growth, but complete cure is uncommon. When obstruction occurs, placement of self-expanding metallic stents using fluoroscopic guidance through a transurethral approach can be a fast and reliable way of establishing urethral patency. The procedure is successful in relieving obstruction in >85% of cases. Stents can also be used to treat urethral strictures.

Cystoscopic-Guided Ectopic Ureter Laser Ablation

Ectopic ureters are a common congenital anatomic deformity in dogs in which the ureteral orifice is located distal to the bladder trigone, in the urethra, vagina, vestibule or uterus. Most ectopic ureters in dogs transverse the bladder intramurally and are candidates for this minimally invasive procedure. Endoscopic repair of ectopic ureters is done with fluoroscopy, ultrasonography, cystoscopy and a diode or holmium;YAG laser.  The abnormal tissue that separates the ureter from the urethra or genital tract is divided longitudinally with the laser from distal to proximal, ending at the level of a normal ureteral termination, so that urine can enter the bladder rather than bypassing it (figure 1). The procedure can be performed in female and male dogs and female cats. Surgical repair of ectopic ureters eliminates incontinence in 30-60% of cases, with failures the result of concurrent urethral sphincter mechanism incompetence (USMI), short urethral syndrome, or an intrapelvic bladder. Laser ablation has similar results, but has the advantage to of being able to be performed at the time of diagnosis and even on an outpatient basis.

Figure 1 – Video demonstrating laser ablation of an ectopic ureter in a dog.

Ureteral Stenting

Figure 2 – Placement of a ureteral stent in a cat. The guidewire for the stent has been passed through the renal cortex, into the renal pelvis, down the ureter, and into the bladder.

Figure 3 – Postperative radiograph of a ureteral stent in a dog, demonstrating the stent’s pigtails in the renal pelvis and bladder.

Ureteral stenting is performed for a variety of disorders to divert urine from the pelvis of the kidney into the urinary bladder. This technique is performed in patients with ureteral obstruction secondary to ureterolithiasis, ureteral or trigonal obstructive neoplasia, strictures, or tears. The presence of a stent results in passive ureteral dilation ( over 2 days to 2 weeks) which may permit the passage of previously obstructive ureteroliths. Stents have a pigtail at either end to maintain their positioning in the bladder and renal pelvis, and come in a range sizes suitable for any dog or cat (figures 2 and 3).

Extracorporeal Shock-Wave Lithotripsy (ESWL) 

ESWL is a minimally invasive alternative for the removal of calculi in the renal pelvis or ureters. The technique uses external shockwaves that pass through a water medium directed in two planes, using fluoroscopic guidance. The urolith is shocked anywhere from 1000-3500 times at different energy levels, causing implosion and powdering of the stone. The debris is then left to pass down the ureter into the urinary bladder over a 1-2 week period. It may take months for full stone clearance and the procedure may need to be repeated.  ESWL can be performed safely for nephroliths larger than 4 mm and smaller than 10 mm.  For larger stones an indwelling double pigtail ureteral stent may be placed prior to ESWL to aide in debris passage via ureteral dilation.

Percutaneous Nephrostomy Tube Placement and Percutaneous Nephrolithotomy (PCNL)

Nephrostomy tubes are locking loop pigtail catheters that may be placed percutaneously to decompress an obstructed kidney and to manage azotemia before proceeding to a prolonged definitive procedure. PCNL can be used to treat renal pelvis or proximal ureteral stones too large to treat with ESWL.

As veterinarians gain experience in the discipline of interventional endourology we find that there are challenges in some of our patients that are not experienced in human endourology. One of these challenges is the feline ureter.  In the healthy state it is a very thin and narrow structure averaging  about  0.4mm in diameter. Ureteral stents for felines are avialbale as small as 2 and 2.5 Fr and for dogs as large as 6 Fr. The obstructed ureter may distend to perhaps a centimeter at its widest point, but usually it is less than that and is often tortuous in nature.  Additionally the cause for ureteral obstructions is often calcium oxalate uroliths which may become embedded in the wall of the ureter making removal impossible, and also making passage of a stent around the stone quite challenging.  Another cause of ureteral obstruction is a stricture at a previous site of urolith lodgment or urolith removal.

Figure 1 – The Tufts team placing the subcutaneous ureteral bypass system using fluoroscopic guidance.

The clinicians and scientists at Norfolk Vet Products have recently patented a device based upon systems used in human medicine to bypass a diseased ureter. This device is the “SUB^TM , a subcutaneous ureteral bypass system.  This system utilizes a locking loop pigtail nephrostomy tube, a subcutaneous vascular access device and a tube cystostomy catheter.

Figure 2 – Fluorscopic image taken immediately following a test injection of a contrast agent into the vascular access port, confirming that there is no leak in the system.

This system brings the surgeon and the internist or interventional radiologist into the same room. It highlights the team approach to veterinary medicine.The device is simple to place. The surgeon isolates the kidney. Using fluoroscopy, the nephrosotomy tube is guided into the renal pelvis, engaged and locked in place (Figure 1). The cystostomy tube is placed in the bladder and sutured in place. A vascular access port is buried subcutaneously and secured to the body wall.  Injection of iohexol contrast agent ensures that there is no leakage at the nephrostomy tube , that the shunt is patent, and that there is no leakage at the cystostomy tube (Figure 2).  Urine flows from the kidney through the shunting port and into the bladder, bypassing the ureter. If the affected ureter is still partially patent, urine may still flow in a natural direction.

Figure 3 – Postoperative radiograph of a cat in which the SUB system has been placed to bypass an obstructed ureter.

Foster Hospital clinicians recently placed this device in a cat that had presented with acute on chronic kidney injury secondary to pyelonephritis, severe ureteritis, chronic kidney disease, nephrolithiasis and ureteroliths. The cat required continuous renal replacement therapy in addition to a prolonged course of antibiotics. He became polyuric after renal replacement therapy had begun; however,  the ureter was so diseased that there was concern about the feasibility of safely passing a stent while maintaining ureteral integrity. A SUB^TM was considered the best option for this patient (Figure 3). The cat is doing well at home with IRIS stage 3 chronic kidney disease with a creatinine of 3 mg/dl.  He is urinating well and has a negative urine culture at this time. Thus far he continues to produce large volumes of urine and the bypass device is working well.

Pathogenesis

Dexmodex canis mites are considered to be normal commensal organisms in the skin, dwelling in hair follicles and sebaceous glands.  It is believed that aberrations of the immune system lead to their proliferation, thus resulting in the development of clinical signs.  Two additional types of Demodex have been described in the literature.  D. injai is a long-bodied mite often found in terrier breeds with greasy coats.  The second is an un-named short-bodied mite; however, molecular testing has shown that this mite may simply be a morphological variant of D. canis.

Juvenile demodicosis develops secondary to an immunocompromised state resulting from endoparasiticism, malnutrition or debilitation.  However, plenty of apparently healthy young dogs present with focal lesions without evidence of systemic illness.  In older animals, endocrinopathies, neoplasia, or chemotherapy may trigger proliferation of Demodex mites.

Clinical features

Demodicosis is categorized as being localized or generalized.  The localized form  (figure 1a and b) carries a good prognosis and most cases spontaneously resolve without medical intervention.  Generalized demodicosis (figure 2) is more severe and may be considered life-threatening in certain cases.  The definition of generalized demodicosis, although a matter of some debate, is the presence of more than four lesions over 2.5cm in diameter.

Lesions often appear on the face and front legs, but progress to involve other sites.  Clinical signs range from erythema, comedones, partial or patchy alopecia in mild cases to furunculosis, crusting, and generalized malaise, lymphadenopathy and fever in more severe cases.  There is almost always a secondary bacterial component associated with demodicosis.

Diagnosis

A deep skin scraping is the current diagnostic method of choice.  A dulled scalpel blade, dental spatula, or curette can achieve acceptable results.  In order to collect the best sample possible, mineral oil should be placed onto the sample site as well as on the sampling instrument to allow for better adhesion of cellular debris.  The skin should be scraped in multiple sites until capillary oozing is noted.  There is a better chance of finding mites in areas where primary lesions are present – such as alopecic areas, or areas where papules, pustules and comedones are found -  than in secondary lesions such as ulcerations.  Once the cellular material has been collected onto a glass slide, a cover slip should be placed and the debris examined under low power (4x or 10x magnification).

Other methods of diagnosis include trichograms (hair plucks), biopsy and histopathology, and impression smears of exudate.  Trichograms are particularly useful for lesions in the periocular and interdigital regions.

Also it is critical to also identify whether a concurrent secondary infection is present.  In severe cases involving furunculosis, bacterial septicemia is a risk if the infection is not addressed.  Staphlyococcus pseudintermedius is most commonly encountered, although Pseudomonas aeruginosa or Escherichia coli may also act as secondary contaminants.

Treatment

Resolution of clinical signs alone is not a reliable endpoint to therapy.  It is important to aim for microscopic cure in addition to clinical cure to obtain long-term remission.  Microscopic cure is defined as negative deep skin scrapings at least twice consecutively, usually one month apart.  It is recommended that treatment continue for one more month beyond microscopic cure.

Amitraz is the only approved therapy labeled for use in dogs with demodicosis.  Protocols vary from daily rinses to weekly rinses using concentrations that vary between 0.025% to 0.06%.  Although amitraz is effective, the author has never used it due to potential side effects – which may affect the owner as well as the patient.  In dogs, amitraz has been reported to cause depression, ataxia, polyphagia, polydipsia, vomiting and diarrhea.  In humans, amitraz anecdotally causes headaches and induces asthma attacks.  The spot-on preparation containing 15% amitraz and 15% metaflumizone is no longer recommended due to its potential to cause a pemphigus foliaceus-like drug reaction.

Ivermectin is not licensed for use in canine demodicosis.  However, studies have shown it to be an effective therapy when used at 0.4-0.6mg/kg orally once daily.  Ivermectin can cause a number of neurological side effects including lethargy, blindness, tremors, mydriasis and death in sensitive dogs.  Collies and herding breeds are most susceptible to ivermectin toxicity, but other breeds can also be affected.  The ABCB1-D1 (MDR-1) gene mutation is considered responsible for acute toxicity in Collies and Collie mixbreeds but is not the only mechanism that causes ivermectin sensitivity.  A test for this gene mutation is available through Washington State University (http://www.vetmed.wsu.edu/depts-vcpl/).

Milbemycin oxime is recommended at a dosage of 1-2mg/kg orally once daily and has a higher safety margin in Collies.  However, dogs with the ABCB1-D1 (MDR-1) gene mutation may still be susecptible to developing ataxia at 1.5mg/kg orally once daily.  Milbemycin is currently unavailable.

Alternative therapies include doramectin administered subcutaneously or orally, or moxidectin in 2.5% spot-on formulation in combination with topical 10% imidacloprid given weekly to bimonthly.  This treatment may be more effective in juveniles with milder forms of disease than in adults with late-onset generalized demodicosis.  Additionally, adjunctive treatments such as shampoo therapy (2-3% benzoyl peroxide or 3-4% chlorhexidine) may provide relief.  Finally, it is imperative that antibiotic therapy is administered concurrent with miticidal therapy.

Monitoring and prognosis 

The long-term prognosis is good as long as the duration of treatment is adequate and underlying systemic disease is addressed.  However, some dogs that have incurable underlying disease may require lifelong pulse therapy such as weekly ivermectin therapy or monthly amitraz dips.  No resistance to treatment has yet been documented in Demodex mites.

Specialized diagnostic and treatment services include: intradermal allergy testing and allergen-specific immunotherapy, biopsy and dermatohistopathology, video otoscopy, myringotomy, and deep ear canal cleaning to name a few. The Dermatology Service also offers in-house consultations and collaborates closely with other specialty departments within the hospital to provide complete and comprehensive medical care for patients.

The Dermatology Service offers appointments at the Foster Hospital Mondays through Saturdays from 9am to 3pm as well as Wednesdays 2pm to 7pm.  We also offer appointments at Tufts VETS in Walpole every Tuesday and Thursday from 8:30am to 4pm.  Equine and other domestic species consults take place on Monday afternoons.

Meet your Dermatology Team:

Lluis Ferrer, DVM, DECVD, PhD – Professor; lluis.ferrer@tufts.edu

Andrea Lam, DVM, DACVD – Clinical Assistant Professor; andrea.lam@tufts.edu

Jillian Czech, CVT – Dermatology Technician (FHSA); vetderm@tufts.edu

Susan Abbott, CVT – Dermatology Technician (Walpole); 508-668-5454

Rosemary Shaughnessey  (FHSA) – Liaison; 508-887-4745