September 2022   |   Volume 20   |   Issue 6

Chronic Enteropathy in Cats

in this issue

in this issue

Chronic Enteropathy in Cats

Osteoarthritis Pain in a Cat

Differential Diagnosis: Icterus in Cats

Canine Intrahousehold Interdog Aggression

Top 5 Preventive Care Tips for Dogs & Cats with Cancer

Hypernatremia in Dogs & Cats

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Welactin CB September 2022

Osteoarthritis Pain in a Cat

Gabriella N. Castro, DVM, The Ohio State University

Arielle Pechette Markley, DVM, cVMA, CCRT, CVPP, DAIPM, The Ohio State University

Nina R. Kieves, DVM, DACVS-SA, DACVSMR, CCRT, The Ohio State University

Orthopedics

|Peer Reviewed

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Osteoarthritis Pain in a Cat

Max, a 15-year-old, 18.2-lb (8.3-kg) neutered male Maine coon, was referred for evaluation of chronic pain attributed to osteoarthritis (OA), which had been diagnosed by the referring clinician 7 months prior. The owner reported Max had trouble ambulating, experienced pelvic limb collapse, and would bite when touched on the caudal end.

Pain persisted despite weight loss and initial management that included administration of compounded gabapentin (12 mg/kg PO every 12 hours for pain management), methimazole (2.5 mg/cat PO every 12 hours to treat previously diagnosed hyperthyroidism), glucosamine/chondroitin (1 capsule [per package label] PO every 24 hours for joint health), polysulfated glycosaminoglycan (2 mg/kg SC every 1-2 weeks as a disease modifying drug for OA), a homeopathic remedy for pain relief, and a nutritional supplement for managing inflammation; cold laser therapy (elbows, hips, and knees) was also used.

Physical Examination

Physical examination was performed with Max under sedation due to his fractious temperament. BCS was 9/9. There was significant disuse muscle atrophy of the pelvic limbs; palpable crepitus in both stifles and elbows; and decreased extension, decreased range of motion, and discomfort on extension of the right hip. The left hip had appropriate range of motion and no crepitus. Crepitus without instability was noted at the level of the stifles. The remainder of the examination was unremarkable.

Diagnosis

Radiographic Findings

Radiographs taken by the referring clinician showed a shallow right acetabulum with decreased coverage of the femoral head and secondary changes, including a sclerotic acetabular rim, smoothly marginated periosteal proliferation along the cranial and caudal pillars of the acetabulum, flattening of the right femoral head, thickening of the femoral neck, and mild craniodorsal subluxation. The left coxofemoral joint was congruent but had mild changes with osteophytes along the cranial acetabular margin. There was a mild amount of spondylosis deformans at L6-L7 and L7-S1.  Radiographs of the stifles showed subchondral bone sclerosis of both medial femoral condyles and medial tibial condyles. Osteophytes and enthesophytes were present along the distal femurs and proximal tibiae. A large amount of amorphous periarticular new bone was located within and adjacent to the craniomedial aspects of the stifle joints and just proximal to the tibial eminences.  Radiographic diagnoses at that time were moderate, right-sided, coxofemoral degenerative joint disease with subluxation of the femoral head; mild, left-sided, coxofemoral degenerative joint disease with no evidence of subluxation; and severe, bilateral stifle degenerative joint disease. At the referral clinic, 8.5 months after initial presentation, Max was sedated, and repeat ventrodorsal and orthogonal lateral pelvic radiographs were obtained to evaluate progression or change (Figure).

Ventrodorsal and lateral pelvic radiographs showing severe osteophyte formation along the right femoral head and neck that caused effacement of the trochanteric fossa. The acetabulum is shallow due to remodeling and osteophyte formation. Mild osteophyte formation remains along the left femoral head and neck, as well as moderate osteophyte formation along the acetabulum. Caudal lumbar spondylosis deformans is unchanged from initial radiographic findings. Rounded, angular mineral bodies are present bilaterally in the stifle joints with moderate concurrent periarticular osteophyte formation. Short, linear mineral bodies can be seen in the soft tissues of the right caudal crus.
Ventrodorsal and lateral pelvic radiographs showing severe osteophyte formation along the right femoral head and neck that caused effacement of the trochanteric fossa. The acetabulum is shallow due to remodeling and osteophyte formation. Mild osteophyte formation remains along the left femoral head and neck, as well as moderate osteophyte formation along the acetabulum. Caudal lumbar spondylosis deformans is unchanged from initial radiographic findings. Rounded, angular mineral bodies are present bilaterally in the stifle joints with moderate concurrent periarticular osteophyte formation. Short, linear mineral bodies can be seen in the soft tissues of the right caudal crus.

FIGURE 1 Ventrodorsal and lateral pelvic radiographs showing severe osteophyte formation along the right femoral head and neck that caused effacement of the trochanteric fossa. The acetabulum is shallow due to remodeling and osteophyte formation. Mild osteophyte formation remains along the left femoral head and neck, as well as moderate osteophyte formation along the acetabulum. Caudal lumbar spondylosis deformans is unchanged from initial radiographic findings. Rounded, angular mineral bodies are present bilaterally in the stifle joints with moderate concurrent periarticular osteophyte formation. Short, linear mineral bodies can be seen in the soft tissues of the right caudal crus.

Ventrodorsal and lateral pelvic radiographs showing severe osteophyte formation along the right femoral head and neck that caused effacement of the trochanteric fossa. The acetabulum is shallow due to remodeling and osteophyte formation. Mild osteophyte formation remains along the left femoral head and neck, as well as moderate osteophyte formation along the acetabulum. Caudal lumbar spondylosis deformans is unchanged from initial radiographic findings. Rounded, angular mineral bodies are present bilaterally in the stifle joints with moderate concurrent periarticular osteophyte formation. Short, linear mineral bodies can be seen in the soft tissues of the right caudal crus.
Ventrodorsal and lateral pelvic radiographs showing severe osteophyte formation along the right femoral head and neck that caused effacement of the trochanteric fossa. The acetabulum is shallow due to remodeling and osteophyte formation. Mild osteophyte formation remains along the left femoral head and neck, as well as moderate osteophyte formation along the acetabulum. Caudal lumbar spondylosis deformans is unchanged from initial radiographic findings. Rounded, angular mineral bodies are present bilaterally in the stifle joints with moderate concurrent periarticular osteophyte formation. Short, linear mineral bodies can be seen in the soft tissues of the right caudal crus.

FIGURE 1 Ventrodorsal and lateral pelvic radiographs showing severe osteophyte formation along the right femoral head and neck that caused effacement of the trochanteric fossa. The acetabulum is shallow due to remodeling and osteophyte formation. Mild osteophyte formation remains along the left femoral head and neck, as well as moderate osteophyte formation along the acetabulum. Caudal lumbar spondylosis deformans is unchanged from initial radiographic findings. Rounded, angular mineral bodies are present bilaterally in the stifle joints with moderate concurrent periarticular osteophyte formation. Short, linear mineral bodies can be seen in the soft tissues of the right caudal crus.

FIGURE 1 Ventrodorsal and lateral pelvic radiographs showing severe osteophyte formation along the right femoral head and neck that caused effacement of the trochanteric fossa. The acetabulum is shallow due to remodeling and osteophyte formation. Mild osteophyte formation remains along the left femoral head and neck, as well as moderate osteophyte formation along the acetabulum. Caudal lumbar spondylosis deformans is unchanged from initial radiographic findings. Rounded, angular mineral bodies are present bilaterally in the stifle joints with moderate concurrent periarticular osteophyte formation. Short, linear mineral bodies can be seen in the soft tissues of the right caudal crus.

Although findings were unchanged from previous radiographs, OA in the right hip appeared mildly progressed.

Differential Diagnoses

Differential diagnoses for decreased range of motion with crepitus in the hip include primary degenerative joint disease, degenerative joint disease secondary to hip dysplasia, fracture (acute or chronic), Legg-Calve-Perthes disease, hip luxation, infective/inflammatory arthritis, and neoplasia.

Bilateral hip dysplasia with secondary OA and bilateral stifle OA were diagnosed based on patient history, physical examination findings, and survey radiographs.

DIAGNOSIS:

HIP DYSPLASIA WITH SECONDARY & STIFLE OSTEOARTHRITIS

Treatment & Management

Max was continued on the medication regimen outlined previously. Rehabilitation was initiated, including acupuncture, low-level laser therapy (12 J/cm2 applied to the lumbar spine, hips, and stifles), pulsed electromagnetic field therapy, soft-tissue techniques (eg, massage, stretching, passive range of motion, joint mobilization), and exercise on an underwater treadmill. Massage and passive range of motion were performed without sedation. 

The first rehabalitation session went well, and weekly sessions were advised. The importance of activity to maintain joint health and encourage weight loss were explained to Max’s owner, and recommendations were made on how to encourage activity at home, including spending more time outside.

Underwater treadmill time and exercises were increased as tolerated; the amount and duration of therapy were dictated by Max’s comfort and willingness to comply. Max had improved hip comfort and range of motion by the third rehabilitation session. He was increasingly comfortable and compliant at each session, and his temperament improved as pain was better controlled by the previously outlined multimodal approach.

Weekly rehabilitation therapy sessions continued, as well as meloxicam (0.04 mg/kg PO every 72 hours; initiated 2 years after rehabilitation therapy was started, extra-label with owner consent), gabapentin (50 mg/cat PO every 12 hours when at home for pain management; 100 mg PO at the time of drop off when coming to the clinic, at least 2 hours prior to the beginning of treatment, as gabapentin is shown to cause the greatest reduction of stress 2 hours postadministration), polysulfated glycosaminoglycan (4.45 mg/kg SC every 7 days), glucosamine/chondroitin (1 capsule [per package label] PO every 24 hours), methimazole (5 mg/cat PO every 12 hours; dose based on thyroid level), acupuncture, low-level laser therapy (12 J/cm2 applied to the lumbar region, hips, and stifles), pulsed electromagnetic field (60 minutes during laser therapy and acupuncture), soft-tissue techniques (eg, massage, stretching, passive range of motion, joint mobilization), underwater treadmill use (intermittent and patient temperament dependent), and therapeutic exercises (variable).1,2

TREATMENT AT A GLANCE

  • Gabapentin and meloxicam can be used to control pain. 
  • Oral glucosamine/chondroitin and polysulfated glycosaminoglycan injections can be administered as supplemental therapy. 
  • Increased activity at home can aid weight loss. 
  • Rehabilitation therapy that includes acupuncture, photobiomodulation therapy (eg, class IV laser), pulsed electromagnetic field therapy, soft-tissue techniques, underwater treadmill use, and therapeutic exercises can be beneficial.

Prognosis & Outcome

Continued therapy and medication helped with long-term control of Max’s pain, enabling comfort and continued mobility gain. 

After 2 years, Max’s weight was 8.4 lb (3.8 kg; 54% decrease from initial presentation); this significant weight loss was likely a key component of improvement. Max ambulated freely in the home, could go up and down stairs, went outside, and played with his feline housemate. He also tolerated being touched on the caudal end and had an improved temperament.

Discussion

Cats and dogs with OA can have different presentations. Dogs often develop OA because of an underlying condition (eg, joint dysplasia, cruciate disease, luxating patellae) that can lead to joint pathology and pain.3 Cats are often presented with primary OA (ie, no underlying disease causing pathology); in one study, a potential underlying cause of OA could only be found in 11% of cats.

Cats often do not show abnormalities related to OA on physical examination, making diagnosis challenging. Diagnosis relies heavily on signs reported by the pet owner5; it is thus important to obtain a thorough patient history and be aware of changes in the patient. Asking specific questions about comfort, jumping, grooming, and activity level at home can help assess for possible signs of OA. Awareness of the unique presentation of OA in cats can help with early diagnosis and treatment. 

Radiographs can help confirm clinical signs that may be attributed to joint disease, monitor changes, and determine the degree of joint disease6; however, survey radiographs may not definitively determine the type of joint disease or inciting cause. Thorough patient history and physical examination are key to diagnosis. Arthrocentesis with cytologic evaluation can help differentiate sepsis, degenerative change, immune-mediated disease, and neoplasia if change is seen on radiographs but the underlying cause is undetermined. 

OA management typically involves weight loss, activity modification with consistent exercise, and pain control. OA cannot be cured or reversed. The goal of treatment should be to manage clinical signs, including adequate pain management, and slow progression.7 Pain should be managed first, so patients can become more active, resulting in weight loss and increased mobility.7

Although NSAIDs are the mainstay treatment in dogs with OA, long-term use is limited in cats in the United States, making pain management in cats with chronic disease challenging. Many older cats with OA have concurrent renal disease, precluding use of an NSAID. 

Alternative medications include gabapentin, tramadol, and amantadine. These drugs in conjunction with disease-modifying agents (eg, polysulfated glycosaminoglycan) and supplements (eg, glucosamine/chondroitin, omega-3 fatty acids) should be considered in cats with OA. Alternative methods of treatment, including rehabilitation, can also play an important role in managing chronic OA.

There are no level 1 evidence studies assessing most oral medications or laser therapy for treatment of OA pain in cats. In addition, there are few FDA-approved long-term medications available to treat OA in cats, making management significantly more challenging than in dogs. 

Frunevetmab, a monoclonal antibody that targets nerve growth factor, has been FDA-approved for use in cats in the United States. Preliminary studies for this new class of pain relievers show possible treatment for feline OA pain.8,9 Clinical trials showed minimal effects on the liver, kidneys, and GI system; dermatologic adverse effects were most common.8,9 Frunevetmab is a monthly injectable medication that may be more easily administered to cats compared with daily oral medications. Further study and evaluation are needed to determine efficacy.

Surgical intervention, including total hip replacement and femoral head and neck ostectomy, is often considered in patients with hip OA, but surgery was not appropriate for this patient because of degenerative stifle changes and severe obesity.

After pain is controlled, activity can be modified to include more low-impact activities, as they are better tolerated by patients with OA. Increasing activity as tolerated should be a goal in sedentary patients.

TAKE-HOME MESSAGES

  • OA is common in overweight, older cats.
  • Feline OA is usually a primary disease process, rather than secondary to disease (eg, hip dysplasia), and routine screening is recommended.
  • OA cannot be cured. Treatment should focus on managing clinical signs and slowing progression.
  • Main principles of OA management are pain control, consistent exercise, and weight loss. 
  • Controlling pain can help increase activity and improve weight control and should be the first step in treatment.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Top 5 Preventive Care Tips for Dogs & Cats with Cancer

Haley J. Leeper, DVM, DACVIM (Oncology), Oregon State University

Oncology

|Peer Reviewed

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Top 5 Preventive Care Tips for Dogs & Cats with Cancer

Cancer management in dogs and cats requires both veterinary specialists and general clinicians. Most patients need continued preventive care from the referring clinician in conjunction with chemotherapy or other treatment from a specialty clinic.

Following are the author’s top 5 preventive care recommendations for cancer patients.

1

Vaccinations

Many vaccinations require regular boosters depending on the patient’s lifestyle and federal and/or state regulations.1 The necessity and effectiveness of vaccinations in patients undergoing chemotherapy has been debated in both human and veterinary medicine.2-5 Patients receiving chemotherapy may not be able to mount an immune response if exposed to an infectious agent, making them more susceptible to infection and warranting vaccination; however, immunosuppression caused by chemotherapy may prevent development of adequate immunity following a vaccination or booster. 

Few veterinary studies have examined the effects of chemotherapy on immune responses, but existing studies found chemotherapy had no effect on pre-existing antibody titers and less impact than expected on T-cell numbers and ability to mount antibody responses.3-5 Differences between these findings and those in human medicine may be due to disparities in chemotherapy dosages in veterinary medicine, species differences, or need for additional research. Some specialists nonetheless advise delaying vaccinations until chemotherapy protocols are completed. 

Antibody titers can be evaluated to determine whether boosters are needed. Uncertainty regarding vaccinations should be discussed with pet owners, and recommendations should be made based on the individual patient. Rabies vaccination is largely regulated by state and local jurisdictions, which may not allow deviation despite concerns about patient health.6 Legal requirements should thus be reviewed during clinical decision-making (see Suggested Reading).

2

Medications & Elective Procedures

Most chemotherapy agents are metabolized and excreted in the body and thus may interact with other medications. 

The author is not aware of evidence-based medicine against the use of flea and tick preventives in chemotherapy patients, and anecdotal experience suggests many preventives are safe to administer during cancer treatment. Tick-borne diseases and heartworm infections in cancer patients can complicate chemotherapy protocols.

Transient bone marrow suppression and delayed wound healing associated with chemotherapy may affect elective procedures (eg, dental prophylaxis, mass removals) often performed in patients with cancer. Timing and necessity of procedures should be discussed with owners.

3

Nutrition

Cachexia, anorexia, hyporexia, cancer diets, and raw food or alternative diets may be discussed during an oncology consultation. Discussion related to these topics is often initiated by the owner.7 

Cachexia is a metabolic syndrome associated with underlying illness and characterized by loss of muscle mass with or without loss of fat.8 Guidelines for nutritional interventions to prevent or treat anorexia and cachexia in veterinary medicine are sparse.8 Patients receiving chemotherapy may experience transient anorexia, but true incidence is not well-defined.9 

In human medicine, cancer diets have been investigated based on research suggesting cancer cells are glucose dependent.10,11 Nutritional recommendations for veterinary patients should focus on nutritionally well-balanced, palatable diets rather than specific formulations because the literature is contradictory and inconclusive.12,13 Owners planning to feed home-prepared meals should first consult a veterinary nutritionist, and owners planning to feed raw diets should be warned of increased risk for pathogen exposure to the immunocompromised patient and members of the household.

4

Supplements & Alternative Medicine

Integrative medicine uses both alternative (eg, herbs, supplements, acupuncture, massage) and allopathic medicine.14,15 

There is very little veterinary oncology literature on alternative medicine. Limited peer-reviewed data are available for use of Yunnan Baiyao and turkey tail mushroom (Coriolus versicolor) for treatment of canine hemangiosarcoma, supplemental liver protectants (eg, S-adenosyl-methionine/silybin A and B) for patients receiving lomustine (ie, CCNU) chemotherapy, and sulforaphane and cannabidiol for treatment of dogs with cancer.16-21 Many of the available studies included small numbers, were only performed on cell lines, and did not administer medications in conjunction with other treatment options. Further studies are needed to understand alternative treatments and potential interactions with allopathic medicine. Consultation with an alternative medicine specialist can be recommended.

5

Diagnosis & Management of Toxicoses & Adverse Effects

General clinicians should monitor patients receiving cancer treatment and report toxicoses and adverse effects to the oncologist so dose adjustments or alternate therapy can be pursued as needed.

Transient bone marrow suppression is a common adverse effect of chemotherapy. Most chemotherapy-induced nadirs occur 7 to 10 days after a maximum-tolerated dose of chemotherapy but can vary.22

CBCs with slide reviews can help monitor RBCs, platelets, and leukocyte/neutrophil counts. A circulating neutrophil count <1,000/µL may indicate the immune system is inadequate to fight infection, and risk for sepsis may be increased.23-25 Prophylactic antibiotics and/or hospitalization may be needed.

Rectal temperature should be measured when obtaining CBC in chemotherapy patients. Hospitalization is recommended in febrile and neutropenic patients. The literature on antibiotic use in cancer patients should be reviewed to ensure judicial use.25,26

Rabacfosadine is FDA-approved for treatment of canine lymphoma and is an increasingly common chemotherapeutic for this cancer; dermatologic toxicoses can be an adverse effect. Dermatopathology manifests as areas of alopecia, hyperemia, moist dermatitis, and/or hyperpigmentation in the inguinal region, trunk, and/or ear canals of dogs that can be confused with routine acute moist dermatitis (ie, hot spots) and ear infections (Figure).27 Steroids should be administered and can be added to the chemotherapy protocol and the rabacfosadine dose reduced.

Conclusion

Cancer patients managed by a specialist also require routine health care management with a general clinician.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Hypernatremia in Dogs & Cats

Edward Cooper, VMD, MS, DACVECC, The Ohio State University

Internal Medicine

|Peer Reviewed

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Hypernatremia in Dogs & Cats
Clinician's Brief
Clinician's Brief

CLINICAL SIGNS OF HYPERNATREMIA

  • Typically only with acute increase in Na+ >170 mEq/L1
  • Largely neurologic manifestations
    • Mentation changes
    • Seizures
  • Chronic changes subclinical
    • Idiogenic osmoles in neurons offset the change in osmolality.

CONSIDERATIONS FOR TREATMENT

  • Treatment is predominantly impacted by underlying cause, acuity versus chronicity, volume status, and need for fluid resuscitation.
  • Address underlying cause when possible.
  • Gradually reduce Na+ to avoid osmotic injury unless change is known to be acute.
    • Maximum rate of change: 0.5-1 mEq/hour
  • Use of a hypotonic fluid is most often required.
  • Serial Na+ monitoring is required every 4 to 8 hours initially, then every 12 to 24 hours once desired change in Na+ is achieved.

CASE EXAMPLE OF PURE WATER LOSS

20-kg patient with Na+ = 160 mEq/L (normal Na+ assumed to be 145 mEq/L)

Free water deficit: 0.6 × BW × (Na+patient/Na+normal − 1) 0.6 × 20 kg (160/145 − 1) = 1.24 L or 1,240 mL

Safe replacement: desired Na+ change/0.5-1 mEq/hour (160 − 145)/0.5-1= 15 to 30 hours

Rate of D5W with correction over 30 hours 1,240 mL/30 hours = 41 mL/hour 

Rate of 0.45% NaCl with correction over 30 hours  (1,240 mL/30 hours) × 2 = 82 mL/hour

CASE EXAMPLE OF HYPOTONIC LOSS

In a 10-kg hypotensive patient with Na+ = 160 mEq/L, an initial fluid resuscitation bolus of 15 mL/kg isotonic BES (Na+ = 140 mEq/L) should be planned for administration over 30 minutes. 

Change in Na+ = (Na+patient − Na+fluid)/(0.6 × BW + 1) (160 − 140)/(0.6 × 10 + 1) = 2.8 mEq per liter of fluid administered

The patient will receive 0.15 L (15 mL/kg × 10 kg) over 30 minutes.  Expected Na+ change is 2.8 mEq/L × 0.15 L = 0.42 mEq/30 minutes or 0.84 mEq/hour; <0.5-1 mEq/hour is considered a safe amount.

BES = balanced electrolyte solution, BW = body weight (in kg), Ca2+ = calcium, CDI = central diabetes insipidus, D5W = dextrose 5% in water, K+ = potassium, Na+ = sodium, NaCl = sodium chloride, NDI = nephrogenic diabetes insipidus, PD = polydipsia, PU = polyuria, USG = urine specific gravity

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Prednisone as Single-Agent Therapy for Dogs with Lymphoma

Alexandria Zabiegala, DVM candidate, Kansas State University

Lisa M. Pohlman, DVM, MS, DACVP, Kansas State University

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Prednisone as Single-Agent Therapy for Dogs with Lymphoma

In the literature

Rassnick KM, Bailey DB, Kamstock DA, et al. Survival time for dogs with previously untreated, peripheral nodal, intermediate- or large-cell lymphoma treated with prednisone alone: the canine lymphoma steroid only trial. J Am Vet Med Assoc. 2021;259(1):62-71.


FROM THE PAGE …

Although lymphoma in dogs is highly responsive to the well-documented CHOP protocol (ie, cyclophosphamide, doxorubicin, vincristine, prednisone), many pet owners opt for therapeutic management with prednisone alone. Prednisone is commonly used as single-agent therapy for lymphoma in dogs, but no prior controlled studies have documented benefits of this treatment.

This study evaluated survival time in client-owned dogs (n = 109) with previously untreated peripheral nodal, cytologically confirmed, intermediate- or large-cell lymphoma treated with prednisone alone. Patients received 40 mg/m2 PO every 24 hours for 7 days and were then maintained at 20 mg/m2 PO every 24 hours; clinicians could increase or decrease the dose at their discretion. 

Owners completed a standardized quality-of-life (QOL) survey on the first day of therapy and at set intervals throughout treatment. Patients were also assessed based on substage at the time of study enrollment (substage a: no clinical signs; substage b: GI signs, respiratory signs, hypercalcemia, fever, hyphema, uveitis) and disease immunophenotype (B cell or T cell). 

Median survival time was 50 days. Although some patients survived >120 days, probability of 6-month survival was 7%. Increased survival time generally correlated with absence of clinical signs (ie, substage a) and high QOL in the first 14 days of the study.


… TO YOUR PATIENTS

Key pearls to put into practice:

1

Although prednisone alone does not provide extended survival time in dogs with lymphoma, it can improve QOL as disease progresses. Prednisone is inexpensive, is easy to administer, and has minimal adverse effects; however, survival times (median, 50 days) are short, and there are negative effects of starting cytotoxic chemotherapy after prednisone administration if the owner reconsiders treatment.

2

Median survival time was most positively correlated with lack of clinical signs at the time of study enrollment and high QOL when treatment was initiated, but not all patients had the same response. Variability in response to any treatment for dogs with lymphoma should be discussed with owners.

3

QOL scoring is valuable for patients with chronic, deteriorating conditions and can be used by clinicians and owners to guide treatment decisions or end-of-life care.

 

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Stability of Ceftazidime in Varying Storage Temperatures

Jason Pieper, DVM, MS, DACVD, Iowa State University

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Stability of Ceftazidime in Varying Storage Temperatures

In the literature

Hoff SE, Berger DJ, Viall AK, Schrunk D, Noxon JO. Chemical and microbiological stability of diluted ceftazidime in three different solutions under three storage temperatures over a 28 day period. Vet Dermatol. 2021;32(5):456-e124.


FROM THE PAGE...

Because otitis externa can be difficult to treat, noncommercial products with minimal supporting evidence, particularly compounded ear medications (made either in compounding pharmacies or the veterinary clinic), are often used. Stability and efficacy of these products can be influenced by several factors (eg, pH, storage temperature). 

This study examined ceftazidime compounded into solutions with 3 base diluents (ie, 0.9% sodium chloride, tris-EDTA, 0.02% phytosphingosine hydrochloride) and stored at 3 temperatures (ie, 77°F [25°C], 39.2°F [4°C], −4°F [−20°C]). Solutions were evaluated against a standard Pseudomonas aeruginosa strain over 28 days for changes in pH, drug concentration, and antimicrobial activity. 

All drug concentrations decreased over time; decrease was more significant when solutions were stored at room temperature compared with being refrigerated or frozen. Drug concentration of the tris-EDTA solution significantly decreased as early as within 7 days, likely due to the higher pH of tris-EDTA compared with other diluents. 

Antimicrobial activity of each solution was affected by time and temperature. Stability was best achieved with the 0.9% sodium chloride solution when refrigerated or frozen. 

This study illustrates the importance of evidence-based medicine in establishing the efficacy of compounded ear medications. For example, ceftazidime diluted into tris-EDTA and stored at room temperature would become unstable within several days, resulting in ineffective treatment.

...TO YOUR PATIENTS

Key pearls to put into practice:

1

Compounding ear medications for clinical use is possible but should only be done with supporting medical evidence.

 

2

Storage temperature and pH can significantly affect the stability of ceftazidime and whether it is active within a solution.

 

3

Compounded drugs have a limited shelf life. Research showing the maximal shelf life for each compounded mixture is important.

Suggested Reading & Author Information

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Effectiveness of Canine Aggression Treatment Protocols

Bonnie V. Beaver, DVM, MS, DSc (Hon), DPNAP, DACVB, DACAW, Texas A&M University

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Effectiveness of Canine Aggression Treatment Protocols

In the literature

Dinwoodie IR, Zottola V, Dodman NH. An investigation into the effectiveness of various professionals and behavior modification programs, with or without medication, for the treatment of canine aggression. J Vet Behav. 2021;43:46-53.


FROM THE PAGE …

Canine aggression studies with large sample sizes are important because aggression, including biting, can be hard to quantify and may reflect breed-related issues.1,2

This study investigated the success of different specialists, techniques, equipment, and medications to manage aggression in dogs. Although defining aggression types in a study can be problematic, the authors used an intragroup approach that accounted for differences in terminology and resulted in 5 broad categories: conflict aggression (ie, aggression toward familiar humans [formerly called dominance aggression]), interdog housemate aggression, fear aggression toward humans, fear aggression toward other dogs, and predatory aggression.

Self-reported data were collected from owners of 963 aggressive dogs. A majority of owners (81%) who sought help from a board-certified behaviorist found the advice helpful for treating their dog’s aggression. Training equipment (eg, antibark collars, muzzles) decreased the probability for successful aggression treatment. Behavior modification training techniques (eg, response blocking) decreased the probability for improvement in fear aggression toward other dogs and predatory aggression. The most consistently beneficial behavior modification techniques included improved dog–owner communication, habituation, relaxation protocols, and short, frequent training sessions. Traditionally prescribed medications (eg, fluoxetine, trazodone) were not helpful, but this may be because owners were not referred early enough to a specialist.

Dogs with fear and anxiety comorbidities were more difficult to treat. In addition, changes in management negatively impacted aggression between familiar dogs, possibly because management changes typically consisted of using time-out, which delays establishment of a stable hierarchy among canine housemates. In contrast, management changes to treat predatory aggression (ie, preventing access to animals that are likely to trigger chasing) are particularly important. 

A clinician was consulted for aggression in 213 (22%) dogs. Of those, 15% were diagnosed with a contributing medical condition, raising suspicion that some dogs not seen by a clinician may have had an undiagnosed contributing medical condition. It is important to ask pet owners about possible behavior problems during routine examinations.


… TO YOUR PATIENTS

Key pearls to put into practice:

1

During routine examinations, it is important to ask dog owners whether the dog is developing unwanted behaviors (eg, aggression), which can be easier to stop when caught early.

 

2

Behavior modification in the form of desensitization and counterconditioning can be useful for managing aggressive dogs.

 

3

Short behavior modification and training sessions are more successful than longer sessions.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


Reference Laboratory Testing: Combating Workplace Stress & Inefficiencies

Reference Laboratory Testing: Combating Workplace Stress & Inefficiencies

Veterinary Trends

|Sponsored

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Reference Laboratory Testing: Combating Workplace Stress & Inefficiencies
Sponsored by Antech

Key Takeaways

  • Antech Diagnostics studied the implications of using in-house laboratories versus reference laboratories, including how this choice affects medicine, workflows, and customer service.
  • Based on the results of the study, using reference laboratories for an increased proportion of testing may improve customer service while reducing staff fatigue and burnout.
  • Neither in-house laboratories nor reference laboratories are the right answer in every situation, and there will always be a need for in-house diagnostic testing for time-critical patients. However, increased use of reference laboratories may serve as a potential solution for some challenges facing practices today.

Burnout and labor shortages are widespread issues in veterinary medicine. Even prior to the COVID-19 pandemic, ≈50% of veterinarians were classified as having high burnout scores,1 and in a 2021 survey, 26% of surveyed veterinarians said they would prefer to work fewer hours, despite the associated pay cut, in order to manage their stress and achieve improved work–life balance.2 In addition, many clinics are operating with fewer credentialed technicians than they would prefer due to a shortage of those professionals.3

Clearly, there is a need for improved efficiency in practice to allow for serving clients with fewer team members and to lessen stress on existing team members. Laboratory testing is one area where small changes can have big impacts on efficiency and the veterinary team. Using the in-house laboratory for wellness testing, including preanesthetic testing, is commonplace, often based on recouping the capital investment in analyzers to justify their expensive cost, but this has significant time demands on the veterinary team. As analyzers have become more affordable over time, it is important to reevaluate workflows in practice and for veterinarians to make individualized recommendations for each patient based on patient and practice factors. Although there will always be a need to run some tests in-house (eg, emergencies or critical patients), sending a greater proportion of tests to a reference laboratory could benefit the entire team, the patient, and pet owner.

THE INVESTIGATION*


“Reference Lab First” Workflows: A Contemporary Approach to Veterinary Diagnostics.

*This investigation has not been published for public viewing. The information presented in this article is raw study data. Study specifics can be found through Antech Diagnostics.

Antech Diagnostics conducted a study to examine the potential impacts of enhanced reference laboratory use on veterinary practices, team members, and clients. Information was collected in a number of ways, with the study broken down into 5 key parts*:

  • Time-motion study
  • Veterinary team survey
  • Pet owner survey
  • Fecal pilot study
  • Economic analysis
Time-Motion Study

Preliminary research on laboratory testing included a medical literature review. Interviews were conducted with veterinarians and key opinion leaders to examine ideas surrounding laboratory testing in practice. Based on this preliminary research, an in-clinic, time-motion study was designed. This portion of the study aimed to quantitatively measure time spent performing in-house diagnostics (ie, hematology, serum chemistry, urinalysis, rapid assays, and fecal parasite examinations). Diagnostic workflows and instrumentation time for in-house and reference laboratory testing were also compared.

This study revealed that it takes ≈30 minutes to receive in-house laboratory results for a typical canine preventive care visit, including a CBC, serum chemistry profile, fecal examination, urinalysis, and rapid assay. Conducting this testing in-house was estimated to increase the length of the typical patient visit by 20 to 30 minutes, impacting both examination room use and client wait times. In particular, it was observed that an average fecal parasite examination takes ≈15 minutes of veterinary technician time (eg, 7 fecal examinations a day equates to 105 minutes of technician time every day).

Veterinary Team Survey

In late 2021 and early 2022, 488 veterinary team members, including veterinarians, veterinary technicians and assistants, and practice managers, were surveyed to understand the reasoning behind where wellness testing is performed, determine preferred methods of communicating results, and identify sources of stress in the clinic. Veterinary team members were also asked about their perceptions of in-house testing as compared with reference laboratory testing in various scenarios. Regarding preanesthetic laboratory testing, 92% of veterinarians surveyed considered blood work performed prior to the day of the procedure acceptable in clinically normal patients, regardless of age.

92% of veterinarians surveyed considered preanesthetic blood work performed prior to the day of the procedure acceptable in clinically normal patients, regardless of age.

When asked about stresses in the veterinary clinic, 78% of respondents reported staffing shortages in at least 1 role (veterinarians or veterinary technicians). In addition, stress levels were reported to be higher during the pandemic and postpandemic as compared with prepandemic. Team members reported an average stress level of 7 out of 10 as compared with a prepandemic level of 5 out of 10.

Pet Owner Survey

In 2022, 1624 pet owners (>800 dog owners, >800 cat owners) were surveyed, with the goal of understanding preferences regarding diagnostic testing. Participants must have sought care for a dog or cat in the last 2 years, have been a primary or shared decisionmaker for their pet’s care, and have been between 18 and 85 years of age.

Of those surveyed, most pet owners were satisfied with their veterinarian and practice. Ninety percent of respondents reported being satisfied with their veterinarian, and 88% were satisfied with their practice overall. On the topic of laboratory testing, 74% said they do not mind waiting until the next day to receive wellness results.

Fecal Pilot Study

In the veterinary team survey, team members noted that ≈50% of all laboratory results obtained in-house are not shared during the client’s visit; instead, for those surveyed, clients are called after their visit with results. The team survey showed that, of the tests performed during a visit, veterinarians felt like clients place the least value on receiving fecal results during the visit. Even when a staff member is available to process an in-house diagnostic sample, these tests, particularly fecal centrifugation and flotation, take considerable time, making real-time results difficult to achieve.

Inspired by these survey results, a detailed pilot study was conducted to examine the effects of transitioning from routine in-house fecal examination to sending fecal samples to a reference laboratory. Impacts of this change on clinic workflow and team member satisfaction were studied; 86% of veterinary associates felt that sending samples to a reference laboratory allowed them to provide better patient care. More than 60% of the practices included in this study were performing passive flotation instead of fecal examination by centrifugation for in-house fecal testing. In contrast, reference laboratories routinely perform centrifugation, contributing to higher accuracy.4

Sending routine fecal examinations to a reference laboratory increased veterinarian job satisfaction by 25% and veterinary assistant job satisfaction by 17%. In addition, 71% of associates reported reduced stress when sending routine fecal examinations to a reference laboratory.

Sending routine fecal examinations to a reference laboratory increased veterinarian job satisfaction by 25% and veterinary assistant job satisfaction by 17%.

Ninety-seven percent of veterinary technicians and 84% of veterinary assistants agreed that sending out fecal examinations improved their practice’s workflows. Sending routine fecal examinations to a reference laboratory is estimated to result in a time savings of 270 to 440 hours per year per clinic.

Economic Analysis

Finally, based on information from earlier portions of the study, an economic analysis looking at the costs of in-house testing versus reference laboratory testing was performed. This analysis was intended to highlight the financial consequences of a transition from routine in-house testing to increased reference laboratory use.

It was found that reference laboratory testing through Antech Diagnostics is typically ≈20% lower in cost than in-house testing. This can result in a higher profit margin for the veterinary practice. When the cost of lower tests and the savings in associate time are combined, changing the practice workflow to focus on reference laboratory usage could increase practice profitability by $120k per veterinarian.

Discussion

This study aimed to examine factors that may influence veterinarian selection of in-house versus reference laboratory testing. In many cases, veterinarians have choices regarding when and how to run laboratory tests; these choices can have significant impacts on practice efficiency and veterinary team satisfaction.

In some cases, the decision of when and where to run a particular test is clear. A panel of experts estimated that ≈20% of veterinary cases are emergent and require in-house diagnostics, whereas ≈25% can only be run by a reference laboratory. However, this leaves ≈55% of diagnostic testing that can either be either run in-house or sent out to a reference laboratory. Addressing this 55% of laboratory tests provides opportunities for veterinarians and practice managers to critically evaluate which approach is best for their practice efficiency, team member and pet owner satisfaction, and profitability. Given the increasing pressure on many veterinary practices, it is important to develop rational protocols regarding laboratory testing.

Veterinary team members may feel some degree of pressure to provide same-day results; however, most clients would prefer a shorter in-clinic visit, followed by a call the next day with laboratory results, as represented by the 74% of pet owners in this study who do not mind waiting until the following day for results on healthy pets and 62% of surveyed owners who do not mind waiting until the next day for results on sick patient visits.

Even in practices that routinely perform in-house laboratory testing, a large portion of in-house testing is not completed by the time the client leaves the clinic. Sending tests to a reference laboratory can take some of the immediate time pressure off veterinarians, giving them a greater opportunity to thoughtfully consider their cases while improving client satisfaction by decreasing appointment time and wait times.

Even in practices that routinely perform in-house laboratory testing, a large portion of in-house testing is not completed by the time the client leaves the clinic.

Submitting routine tests to a reference laboratory can free up significant staff time and clinic resources, which is critical, considering 78% of clinics are experiencing staffing shortages. Simply sending routine fecal samples to a reference laboratory for parasite examinations can free up nearly 2 hours of technician time per day, which can be used to perform other tasks, allow for a more relaxed work pace that decreases stress levels and reduces staff burnout risks, and potentially increase practice profitability.

Finally, reference laboratory tests can result in a 20% savings as compared with in-house testing. This cost savings, in addition to the time savings offered, can further contribute to practice profitability. This may be in contrast to the perceived reality for some clinics, as cost profiles have changed over time.

Implications for Practice

Sending samples from wellness visits and nonemergent sick patient visits to a reference laboratory can streamline workflows while also improving client satisfaction, staff satisfaction, and practice profitability.

Most clients are happy to wait until the next day for laboratory results for annual wellness testing, preanesthetic blood testing, and some mild illnesses. Although in-house testing may seem more convenient for the client, it increases the length of the client’s visit, and clients still may not receive results until the following day. Utilizing a reference laboratory when indicated can enhance client satisfaction (by reducing the time they must spend waiting in an examination room for results) without negatively impacting patient care.

Fecal parasite testing is an example of a diagnostic test that requires a high investment of staff time and training and has low staff enjoyment scores. Using a reference laboratory for routine fecal examinations frees up staff to handle other tasks, which can help reduce the risk for burnout and alleviate some staffing shortages. In most cases, submitting tests to a reference laboratory is also significantly less expensive to the practice than running tests in-house, especially when savings on veterinary technician time are factored in.

If sending routine tests to a reference laboratory can lead to improvements in both staffing and profitability while reducing stress and improving client experience, this is an easy step to take towards efficiency in the typical veterinary practice.


EXPERT COMMENTARY

Designation of veterinary medicine as an essential service during the pandemic kept veterinarians and other team members employed and allowed pets to get needed care, but it came at a cost. Many practices were overwhelmed with client demands, client wait times were longer, and demands on the veterinary team resulted in increased work stress. Staff shortages and hiring difficulties have made solving these problems harder, making a focus on practice efficiency essential.

The results of this study revealed many opportunities for improving diagnostic workflows. One area worth exploring is timing of preanesthetic blood work; 92% of veterinarians consider preanesthetic blood work performed prior to the day of the procedure acceptable in clinically normal patients. Shifting away from day-of, in-house testing may improve efficiency. Of course, each practice will need to decide how far out the testing can be done and how to integrate earlier testing with client convenience.

Of the surveyed pet owners, 74% were willing to receive wellness results the next day; this means test result communications can be grouped together and sent via email or text and done at a time most convenient for the practice, which can free up staff time for other tasks.

Making it easier for team members to do their jobs obviously increases team job satisfaction and reduces work stress, both of which can lead to better employee retention. These results particularly demonstrated that fecal testing is a great example of a diagnostic test that requires a high investment of staff time and training and has low enjoyment scores.

Neither in-house nor reference laboratory testing is the right answer in every situation, but the challenges facing practices these days make it more important than ever to evaluate which should be used with what kind of testing and what kind of case.—Karen E. Felsted, CPA, MS, CVPM


*This investigation has not been published for public viewing. The information presented in this article is raw study data. Study specifics can be found through Antech Diagnostics.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


Research Note: Snail Mucus for Treatment of Canine Atopic Dermatitis

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Management of canine atopic dermatitis requires a multimodal approach that includes allergen-specific immunotherapy, antipruritic medications, barrier restructuring agents, and skin and coat care. New therapeutic approaches may minimize the need for broad-spectrum therapies (eg, glucocorticoids, cyclosporine) and enable targeted, natural treatment. Mucus from snails (ie, Helix aspersa Müller) is rich in substances (ie, hyaluronic acid, mucopolysaccharides, polyphenols, bioactive minerals) that act as a protective barrier to the skin and counteract damage associated with oxidative stress.1 

This in vitro study investigated use of a snail mucus filtrate to modulate expression of inflammatory mediators (eg, cytokines) for treatment of canine atopic dermatitis. Mucus significantly reduced release of interleukin-6, -8, and -17A and inhibited expression of tumor necrosis factor-alpha in cell lines of canine epidermal keratinocytes. Snail mucus filtrate may potentially be useful for management of canine atopic dermatitis.

Source & References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Buprenorphine CB September 2022

Failure of Radioiodine Therapy in Cats with Hyperthyroidism

Alex Gallagher, DVM, MS, DACVIM (SAIM), University of Florida

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Failure of Radioiodine Therapy in Cats with Hyperthyroidism

In the literature

Mullowney D, Chang Y, Glanemann B, Syme HM. Treatment failure in hyperthyroid cats after radioiodine (I-131) injection. J Vet Intern Med. 2021;35(4):1688-1696.


FROM THE PAGE…

Hyperthyroidism is common in cats, and various treatment options are available, including medication, diet, surgery, and radioactive iodine (RAI; ie, I131) therapy. RAI therapy is considered the treatment of choice because it is minimally invasive and typically achieves a permanent euthyroid state. RAI therapy has resolved hyperthyroidism in ≈95% of cats after a single treatment.1

This study evaluated the outcomes of cats with persistent hyperthyroidism 2 to 4 weeks after receiving RAI therapy and assessed for predictors of ultimate treatment failure. Out of 959 treated cats, 121 continued to have hyperthyroidism (total thyroxine [tT4] concentration, >3.1 µg/dL) 2 to 4 weeks after treatment; initial failure rate was 12.6%. Of these 121 cats, 87 had sufficient follow-up information, with 35 subsequently having tT4 <3.1 µg/dL without further treatment. Most of the 35 cats achieved tT4 concentration <3.1 µg/dL within 6 months (median, 8 months; range, 3-13 months).

Fifty-two cats continued to have hyperthyroidism after RAI therapy, and treatment was considered a failure; this failure rate (ie, 5.6%) is similar to previously reported rates.2-5 Twelve of the 52 cats subsequently underwent thyroidectomy, of which only 4 showed resolution of hyperthyroidism. Of these 12 cats, 5 had thyroid carcinoma, 5 had adenoma, and 2 did not have histopathology.

Repeat RAI therapy was performed in 14 of the 52 cats in which treatment had failed, including one cat with failed thyroidectomy. Ten of the 14 cats had tT4 concentration <3.1 µg/dL after repeat RAI therapy, and 2 cats later became euthyroid without further treatment, suggesting repeat RAI therapy can be successful in cats after initial treatment failure.

Higher tT4 concentration at time of discharge and a higher weight-normalized RAI dose (ie, RAI dose divided by body weight) were independently predictive of treatment failure. tT4 concentration >11.6 µg/dL had a 100% specificity for predicting failure.


…TO YOUR PATIENTS

Key pearls to put into practice:

1

RAI therapy successfully treats feline hyperthyroidism in ≈95% of cases and is generally considered the treatment of choice.

 

2

Approximately 40% of cats that remain hyperthyroid after an initial dose of RAI may have tT4 concentration <3.1 µg/dL in a median of 8 months and not require further therapy. Cats may need to be monitored for ≥6 months after RAI therapy before repeat therapy is considered.

3

Treatment failure is likely in cats with posttreatment tT4 concentration >11.6 µg/dL, and repeat RAI therapy should be considered earlier than 6 months.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Credelio CB September 2022

Research Note: Sildenafil Hydrogel for Wound Healing in Dogs

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Sildenafil is a phosphodiesterase-5 inhibitor that enhances tissue blood flow via vascular smooth muscle relaxation and stimulates nitric oxide release, which is beneficial for wound healing. Topical sildenafil is safe, nontoxic, and nonirritating for treatment of wounds in various noncanine species.1,2 

This study evaluated the effect of a novel topical sildenafil citrate hydrogel on wound healing in dogs. Six dogs with 4 excision wounds each along the dorsum were administered a hydrogel containing 0%, 5%, or 10% sildenafil or a nonadherent bandage every 24 hours for 21 days. Daily topical sildenafil resulted in systemic concentrations that may have been in the therapeutic range for pulmonary hypertension in 3 dogs (1 dog at day 14 and 2 dogs at day 21), but plasma concentrations remained within safe ranges. Topical sildenafil promoted early granulation formation; however, additional research is needed to determine the most effective hydrogel formulation, as well as ideal timing and frequency of application.

Source & References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Trupanion CB September 2022

Transdermal Gabapentin Use in Cats

Sheilah A. Robertson, BVMS (Hons), PhD, DACVAA, DECVAA, DACAW, DECAWBM (WSEL), CVA, MRCVS, Lap of Love Veterinary Hospice, Gainesville, Florida

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Transdermal Gabapentin Use in Cats

In the Literature

Slovak JE, Costa AP. A pilot study of transdermal gabapentin in cats. J Vet Intern Med. 2021;35(4):1981-1987.


FROM THE PAGE…

Gabapentin is widely used in cats to decrease fear and stress and treat some painful conditions (eg, osteoarthritis). Oral administration can be difficult in cats and can lead to treatment failure; less invasive administration methods are thus desirable. The transdermal route is used for mirtazapine, and an FDA-approved formulation is available; however, not all molecules are suitable for transdermal administration and should be evaluated in the target species. 

This study reported the use of gabapentin in a proprietary base and its ability to traverse feline skin using an in vitro diffusion cell model, as well as an in vivo study on client-owned cats (Table). The in vitro study confirmed that the formulation traverses cadaver skin.

TABLE

In Vivo Phase of the Transdermal Gabapentin Study

Age Group Concentration (mg/mL) Dose Interval Application Site Treatment Duration (days)
<6 years of age (n = 8) 250 5 or 10 Every 8 hours Inner ear pinna or shaved cervical skin 5
>8 years of age (n = 15) 250 10 Every 8 hours Inner ear pinna 5

Blood samples were collected before administration of the first dose and on days 1 and 5. In cats <6 years of age, there were no significant differences in serum concentrations of gabapentin between the 2 doses or sites of application. In cats >8 years of age, serum concentrations were significantly higher on day 5 versus day 1. Serum levels were at least 6 times lower compared with published values after oral administration.1 

Pain scores were reported for cats >8 years of age, but the type of pain was not included. Pain in this age group would likely be chronic (maladaptive); therefore, the acute pain scoring tools used in this study were not appropriate. Gabapentin can cause sedation, which may interfere with pain scoring, but details on sedation were not provided. 

Results of this study demonstrated low levels of gabapentin in blood after transdermal application. No conclusions should be drawn about analgesic efficacy from the data provided. Sedation scores were not provided, and the first sample was collected one day after application was started; thus, usefulness of this transdermal application prior to in-clinic visits is unknown.

…TO YOUR PATIENTS

Key pearls to put into practice:

1

Additional studies are needed before transdermal formulations of gabapentin can be reliably used before visits to the clinic or for maladaptive pain in cats. Compounded products are not subjected to safety or efficacy evaluations.2

2

Oral formulations of gabapentin produce sedation and decrease fear in most cats. Maximum plasma concentrations are reached in 1 to 2 hours.

 

3

In a survey, 71% of clinicians reported oral gabapentin as the first drug used to treat chronic musculoskeletal pain.4 A small study of cats with osteoarthritis supports this use.5

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Zenalpha CB September 2022

Point-of-Care Lung Ultrasonography for Diagnosis of Pulmonary Contusions

Britt Thevelein, DVM, DACVECC, University of Georgia

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Point-of-Care Lung Ultrasonography for Diagnosis of Pulmonary Contusions

In the Literature

Dicker SA, Lisciandro GR, Newell SM, Johnson JA. Diagnosis of pulmonary contusions with point-of-care lung ultrasonography and thoracic radiography compared to thoracic computed tomography in dogs with motor vehicle trauma: 29 cases (2017-2018). J Vet Emerg Crit Care (San Antonio). 2020;30(6):638-646. 


FROM THE PAGE …

Pulmonary contusions are common in patients that have sustained vehicular trauma; however, these injuries may be initially underdiagnosed because they may not be associated with obvious abnormalities on physical examination. Moreover, conventional radiographic signs of pulmonary contusion often lag behind clinical signs. In humans, thoracic CT is the gold standard for diagnosing pulmonary contusions, although lung ultrasonography is also highly sensitive. In veterinary medicine, financial concerns and sedation requirements may limit the use of CT; less-expensive options should thus be explored. Lung ultrasonography is relatively inexpensive, minimally invasive, rapid, and available in many clinics.

In this study, regionally based lung ultrasonography, 3-view thoracic radiography, and thoracic CT were performed on 29 dogs following vehicular trauma. The lung-ultrasound protocol (veterinary bedside lung ultrasound examination [ie, Vet BLUE]1) consisted of evaluation of the caudodorsal, perihilar, middle, and cranial lung regions on both sides of the thorax (8 regions total). These regions were evaluated for B-lines (ie, lung rockets) and C-lines (ie, shred sign)—artifacts that represent interstitial syndrome (ie, wet lung). The presence of these artifacts following blunt-force trauma are suggestive of pulmonary contusions.2 

Findings indicated that lung ultrasonography has a higher sensitivity than radiography for diagnosing pulmonary contusions when compared with thoracic CT, suggesting lung ultrasonography should be performed as part of trauma triage examination for rapid diagnosis of pulmonary contusions.


… TO YOUR PATIENTS

Key pearls to put into practice:

1

Thoracic ultrasonography is useful during triage examination of a trauma patient for rapid diagnosis of pulmonary contusions, pneumothorax, and pleural effusion.

 

2

Thoracic radiography is not sensitive enough to diagnose pulmonary contusions but may be useful in a later stage for identifying other trauma pathology (eg, fractures, diaphragmatic hernia).

 

3

Pneumothorax may interfere with assessment for B- and C-lines on thoracic ultrasonography. In addition, B-lines should be interpreted with caution in patients with prior lung disease, as they may represent lung pathology other than pulmonary contusions.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Synovetin CB September 2022

Prognosis & Risks of Large Intestinal Surgery in Cats

Heather L. Troyer, DVM, DABVP, CVA, CVPP, Oradell Animal Hospital, Paramus, New Jersey

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Prognosis & Risks of Large Intestinal Surgery in Cats

In the literature

Lux CN, Roberts S, Grimes JA, et al. Evaluation of short-term risk factors associated with dehiscence and death following full-thickness incisions of the large intestine in cats: 84 cases (1993-2015). J Am Vet Med Assoc. 2021;259(2):162-171.


FROM THE PAGE…

Dehiscence is a critical surgical complication. Large intestinal incisions may be prone to dehiscence due to poor collateral blood supply, high bacterial load, and high intraluminal pressure during fecal bolus passage.

This retrospective study evaluated 84 cats that underwent full-thickness incisions of the large intestine during various procedures, including subtotal colectomy with preservation of the ileocolic junction and colorectal anastomosis, total colectomy (including the ileocolic junction and enterorectal anastomosis), partial colectomy with colocolic anastomosis, partial colectomy with ileocolic resection and jejunocolic anastomosis, partial colectomy with ileocolic resection and ileocolic anastomosis, and colonic biopsy or colotomy. Reasons for colonic biopsy included chronic vomiting, diarrhea, recurrent colitis with rectal prolapse, and hematochezia.   

Factors associated with dehiscence included hypoalbuminemia, renal dysfunction, administration of blood products or >2 classes of antimicrobials, and intra-abdominal fecal contamination. Anorexia was the only clinical sign associated with intestinal dehiscence. 

Factors identified as predictors of dehiscence and nonsurvival to hospital discharge included the presence of band neutrophils, administration of blood products, partial colectomy with colonic resection and anastomosis, postoperative inflammation or infection of the skin incision, and postoperative cardiopulmonary arrest. 

Factors associated with nonsurvival to hospital discharge only included low serum globulin concentration, repair of colonic trauma or dehiscence, and postoperative colonic dehiscence.

Complications were uncommon in cats undergoing surgery due to megacolon. No association was found between histologic diagnosis of malignancy or inflammation and survival to discharge or intestinal dehiscence. 

These findings suggest that cats with systemic disease may be at increased risk for postoperative dehiscence compared with cats with focal disease.


…TO YOUR PATIENTS

Key pearls to put into practice:

1

Identifying feline patients as low risk for colonic surgery may improve surgical outcome. Stabilization, diagnosis, and preoperative treatment of cats at higher risk may also improve the outcome.

2

Referral to a board-certified surgeon is likely to improve survival. This study only evaluated cases treated by board-certified surgeons from tertiary institutions, which may have better resources and more consistent overnight care.

3

Pet owners should understand colonic surgery is a last resort because of the inherent risks of surgery on an organ with a high bacterial load, different vasculature, and intermittently high intraluminal pressure. Surgery can, however, be an appropriate alternative to failed medical management in some cases.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Shots for Good CB September 2022

Repeat Radiography: The Mechanical Obstruction Dilemma in Veterinary Patients

James Howard, DVM, MS, DACVS, The Ohio State University College of Veterinary Medicine, Columbus, Ohio

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Repeat Radiography: The Mechanical Obstruction Dilemma in Veterinary Patients

In the literature

Miles S, Gaschen L, Presley T, Liu CC, Granger LA. Influence of repeat abdominal radiographs on the resolution of mechanical obstruction and gastrointestinal foreign material in dogs and cats. Vet Radiol Ultrasound. 2021;62(3):282-288.


FROM THE PAGE …

Distinguishing mechanical obstruction from functional ileus can be challenging. Radiography is commonly used to evaluate intestinal obstructions, but ultrasonography is used in some clinics and has greater sensitivity than radiography for detection of small intestinal obstructions.1,2 Radiographic features of obstruction include variability in small intestinal diameter, visualization of foreign material, and gas pattern abnormalities.1-4 Clinical signs should be considered in conjunction with subjective appearance of the bowel.5 

This retrospective study aimed to determine the incidence of radiographic resolution (ie, absence of foreign material, movement of foreign material into the colon, absence of previously diagnosed intestinal dilation) of obstruction or GI foreign material with medical management. Radiography was repeated within 36 hours of initial radiography, and resolution was 26.8%. A second repeat set of radiography performed 36 hours after initial radiography had resolution of 34.6%, and resolution was 50% following a third repeat set of radiography; however, there was no statistical difference in resolution between the second and third sets. 

Foreign material was definitively diagnosed in 46.4% of cases; 29.6% of which were resolved with medical management. A similar rate of resolution (35.5%) was noted in cases with questionable foreign material. When specific dilation patterns were examined, 37.5% of resolved cases were gastric only. Only 17.1% of patients with small intestinal dilation and mechanical ileus had resolution, and only 11.4% of patients with both small intestinal and gastric dilation had resolution. Anatomic location of foreign material was not a significant predictor of resolution.

These results offer a helpful indicator of timing for surgical intervention, as it is illustrated that multiple radiographs 36 hours after an initial study provided no difference in resolution when compared with first repeat radiographs taken within 36 hours of the first study. Lack of radiographic improvements in conjunction with clinical signs and holistic patient evaluation can indicate surgery should be performed earlier, as opposed to pursuing additional radiography.


… TO YOUR PATIENTS

Key pearls to put into practice:

1

Repeat radiography may be necessary if a mechanical obstruction is not conclusively present: one additional set within 36 hours is recommended. At this author’s institution, repeat radiography within 12 to 18 hours is standard. Surgical exploration is generally recommended when there is radiographic evidence and/or clinical signs of a mechanical obstruction.

2

Definitive diagnosis of foreign material is made in ≈50% of patients. Clinical signs, patient history, and repeat imaging are paramount to determine surgical candidacy.

 

3

Pet owner education is important, as continued diagnostics and medical management incur additional costs. Owners should understand that only ≈30% of patients with clinical signs or suspected mechanical obstruction show radiographic resolution, regardless of whether foreign material is definitively detected.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Research Note: Pseudomonas aeruginosa in Nonmedicated Dog Grooming Products

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Pseudomonas aeruginosa is the most commonly isolated bacteria in dogs with postgrooming furunculosis and is often found in human hair and skin care products, leading to possible risk for infection in consumers.1-3 This study investigated prevalence of and risk factors for P aeruginosa contamination in nonmedicated dog grooming products. Products used by grooming salons (n = 97) and pet owners (n = 20) were cultured, and potential risk factors (ie, bottle size, relative remaining volume, content dilution, expiration date, ingredient list) were recorded. P aeruginosa was identified in 14 out of 117 samples, and diluted products were contaminated significantly more often than nondiluted products. Other potential risk factors were not significantly associated with contamination. Product dilution is associated with contamination and may increase the risk for bacterial skin infection in exposed dogs.

Source & References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

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Alternative Protocol for Feline Diabetic Ketoacidosis (DKA)

Thomas Schermerhorn, VMD, DACVIM (SAIM), Kansas State University

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Alternative Protocol for Feline Diabetic Ketoacidosis (DKA)

In the Literature

Zeugswetter FK, Luckschander-Zeller N, Karlovits S, Rand JS. Glargine versus regular insulin protocol in feline diabetic ketoacidosis. J Vet Emerg Crit Care (San Antonio). 2021;31(4):459-468.


FROM THE PAGE…

Diabetic ketoacidosis (DKA) is a complicated presentation of diabetes characterized by hyperglycemia and hyperketonemia. Cats with DKA are often presented with severe metabolic disturbances, including volume deficit, electrolyte abnormalities, and metabolic acidosis. Affected cats are often critically ill on presentation and require aggressive treatment to survive. 

Principal goals when beginning treatment should include volume replacement and administration of insulin to address hyperglycemia and arrest ketone production, which has traditionally been achieved using a short-acting insulin formulation administered via intermittent injection or CRI. Various protocols using regular or another short-acting insulin formulation with or without the addition of insulin glargine have been successfully used to treat DKA in cats.

This study compared 2 insulin protocols for the initial treatment of cats with DKA. Standardized clinical criteria were used to diagnose DKA in 20 cats. Cats were then randomly selected to receive either a standard regular insulin CRI or an alternative protocol of insulin glargine given via intermittent injection (basal-bolus protocol). Insulin glargine was initially given at 2 Units/cat SC, then given at 1 Unit/cat IM after 2 hours, and continued at 1 Unit/cat IM every 4 hours if glucose remained >250 mg/dL.

Time between initiation of insulin treatment and improvement in hyperglycemia was significantly shorter in cats receiving the basal-bolus glargine insulin protocol; hospital stay was also significantly shorter compared with cats receiving only regular insulin. Although there was no difference between protocols for time to resolution of ketonemia, which was the main outcome the study intended to measure, the study may have been underpowered to make this determination.

Studies that examine clinically relevant outcomes following specific interventions are needed in veterinary endocrinology. Regular insulin given via CRI (alternatively, via intermittent injection) is the most common protocol for early insulin replacement in cats with DKA. Other short-acting insulins (eg, insulin lispro) as a CRI or intermittent injection have been reported, however, and several studies had good outcomes with use of a long-acting insulin (usually glargine).1-3

…TO YOUR PATIENTS

Key pearls to put into practice:

1

Basal-bolus administration of insulin glargine offers a useful alternative to CRI administration of regular insulin.

 

2

Higher costs associated with insulin glargine may be offset by faster clinical improvement and shortened hospital stay. For cats managed with glargine, the insulin prescribed for in-hospital use can be dispensed for at-home use.

3

The glargine protocol in this study appears to be safe and effective for controlling hyperglycemia and hyperketonemia in cats with DKA. Regardless of the insulin protocol selected, success requires effective management of fluid balance, electrolyte disturbances, acidosis, and any concurrent disorders.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Canine Intrahousehold Interdog Aggression

Ellen Lindell, VMD, DACVB, Veterinary Behavior Consultations, Asheville, North Carolina

Behavior

|Peer Reviewed

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Canine Intrahousehold Interdog Aggression

Betty, a 2-year-old, 55-lb (25-kg) crossbreed dog, is presented for aggression toward her housemate, Sam, a 2-year-old, 57-lb (26-kg) neutered male crossbreed hound. Betty was adopted at one year of age. Four months after adoption, Betty began lunging at Sam when he walks near her while she is at rest and when both dogs attempt to walk through a doorway together, often when leaving and re-entering the house. She also snaps at her owner during attempts to move her away from the window while barking.

Physical examination, CBC, serum chemistry profile, and total thyroxine results are within normal limits.

Betty is diagnosed with intrahousehold interdog aggression: social conflict-related, as well as redirected aggression toward her owner. Social conflict-related aggression typically includes frustration-related behaviors and anxiety; redirected behaviors can be frustration based.

Which of the following drugs would be appropriate for this patient?*

Do Not Use Proceed with Caution Safe

The following represents the best responses based on drug metabolism, pharmacokinetics, species, diagnostic differentials, clinical and laboratory data, and other pertinent findings.

FLUOXETINE

Correct ResponseSafeFluoxetine is a selective serotonin reuptake inhibitor (SSRI) that can reduce signs of anxiety and frustration. SSRIs block the reuptake of serotonin, increasing serotonin availability in the synaptic cleft.1 Although fluoxetine can be useful in dogs with aggressive behavior during social conflict, this drug is not ideal in dogs with reduced liver function because it is highly metabolized in the liver, has a long half-life, and has active intermediate metabolites.

Reduced appetite is common. Behavioral adverse effects can include irritability (eg, increased aggression when disturbed while resting), increased anxiety (eg, hypervigilance, pacing), social withdrawal (eg, increased time away from members of the household), and/or hypersensitivity to sound (eg, increased startle response). Although these effects can be transient, they can exacerbate social conflict between humans and pets and may warrant cessation of medication. Anecdotally, play behavior is reduced in some dogs, and this should be considered when treating intrahousehold aggression, as play can help maintain healthy relationships between dogs.

Information regarding safety and dosages is available, and there is clinical and anecdotal support for use of fluoxetine to treat behavioral disorders in dogs.2-6 Fluoxetine is FDA-approved for treatment of separation-related anxiety. Any other use is extra-label.

PAROXETINE

Correct ResponseSafeParoxetine is an SSRI used in humans to manage anxiety, particularly social anxiety. Recommendations for use in dogs with social anxiety are based on anecdotal reports and extrapolation from human literature.7

Pet owners often report an increase in positive social interactions (eg, play) after paroxetine administration. This drug is rapidly metabolized by the liver and does not have active metabolites and thus may be preferable in dogs with underlying medical conditions.

Behavioral effects of SSRIs typically overlap; therefore, drug selection should be based on tolerance of adverse effects. Constipation is common due to mild anticholinergic activity. Urinary retention is common in cats but not in dogs. Paroxetine should not be a first-choice treatment in patients with history of lower urinary tract disease with dysuria.

VENLAFAXINE

Correct ResponseProceed with CautionVenlafaxine is a serotonin and norepinephrine reuptake inhibitor (SNRI; a class of drugs that targets serotonin and norepinephrine). SNRIs are typically only considered in patients with inadequate response to SSRIs. SNRI effects on norepinephrine could help reduce impulsivity that contributes to redirected aggression. Venlafaxine use in veterinary patients is based on human studies and anecdotal information; a small study on use of venlafaxine in cats is available.8

Dosages, adverse effects, and safety parameters in dogs are not well established9; regular monitoring for adverse effects is therefore needed. Venlafaxine affects the cardiovascular system, potentially triggering tachycardia, and should be used with caution in patients with history of cardiac disease. Premedication screening should include baseline laboratory work (eg, CBC, serum chemistry profile) and assessment of cardiac health. Owners should be made aware that physical and laboratory parameters need to be monitored during treatment.

CLOMIPRAMINE

Correct ResponseProceed with CautionClomipramine is a tricyclic antidepressant that enhances transmission of serotonin and norepinephrine and can help manage anxiety and frustration-related behaviors in dogs.10-13

Although clomipramine is typically well tolerated in dogs, the potential for adverse effects is greater with tricyclic antidepressants than with SSRIs. Adverse effects can include GI signs, seizures, and exacerbation of cardiac arrhythmias, particularly bradycardia. Pretreatment screening should assess liver and kidney function, thyroid function, and cardiac rhythm. Monitoring should continue for the duration of therapy. Some dogs experience mild sedation, likely due to the drug’s anticholinergic properties.

An FDA-approved form of clomipramine is available for treatment of separation-related anxiety in dogs. Any other use is extra-label.

BUSPIRONE

Correct ResponseDo Not UseBuspirone is a partial serotonin agonist that can reduce anxiety in dogs. This drug is not typically effective as a single agent and is more often used to augment the effect of SSRIs, particularly in the treatment of refractory generalized or context-specific anxiety. Serotonin syndrome, a reaction to excessive serotonin, can occur when serotonergic medications are combined. Signs of serotonin syndrome typically develop acutely and can include agitation, GI signs, cardiac signs, seizures, hyperthermia, and death; combination use should only be after risk assessment. Disadvantages of buspirone use include latency to effect and need for frequent administration.

Physical and behavioral adverse effects in dogs are rare. Buspirone is not helpful for managing aggressive behavior and can result in increased aggression in cats14; monitoring may thus be needed.

TRAZODONE

Correct ResponseProceed With CautionTrazodone is a serotonin antagonist and reuptake inhibitor that can be used to reduce anxiety and arousal and is used in humans to improve sleep. The dose for relieving anxiety may differ from the dose for sleepiness or sedation and can be adjusted as needed. Trazodone may be less useful than SSRIs for chronic therapy because it has a short half-life and sedation is a common adverse effect; however, trazodone is well tolerated as an event drug.15-17 Cardiac and liver function should be monitored before and during chronic treatment.14

Behavioral effects can fluctuate, be unpredictable, and potentially cause problems for patients with intrahousehold interdog aggression; trazodone may not be helpful for these patients. The sedative effects of trazodone can also contribute to reduced engagement in positive social interactions (eg, play). Occasional aggression has been reported with this drug.18

Trazodone can be considered adjunct therapy if given to avoid sedation and used in conjunction with SSRIs; serotonin syndrome is unlikely but can occur with coadministration of trazodone and SSRIs.

CLONIDINE

Correct ResponseSafeClonidine is an alpha-2 agonist used for treatment of hypertension, anxiety, and impulsivity.19 Pretreatment screening should assess liver and kidney function, blood pressure, and cardiac health. Blood pressure should be measured every month for 3 months after therapy is initiated, then every 6 months for the duration of therapy.

Although clonidine alone is not generally used to treat behavioral disorders, it can be used in conjunction with SSRIs in dogs with signs of frustration and anxiety. Clonidine may help reduce redirected aggression and reaction time during social conflict; however, sedation is possible. Clonidine is a hypotensive agent that should be tapered if sedation occurs, even at a low dose, to avoid abrupt changes in blood pressure after long-term administration.

GABAPENTIN

Correct ResponseProceed with CautionGabapentin is an anticonvulsant that binds to the alpha-2-delta subunit of calcium channels and can reduce anxiety. This drug is generally used as a long-term augmenting agent in conjunction with SSRIs. Some patients exhibit sedation or ataxia with minimal relief of anxiety, particularly when given higher doses. Chronic administration of gabapentin is not a first choice for patients that do not have high levels of anxiety in the home and in which sedation is not desirable. Pending response to other medications, a gabapentin trial may be considered to manage territorial barking, which is mostly frustration-related behavior but can also be associated with anxiety. Gabapentin is safe for use in combination with most psychopharmaceutical agents. Renal function should be monitored before and during treatment, as gabapentin is renally excreted.

ACEPROMAZINE

Correct ResponseDo Not UseAcepromazine is a phenothiazine tranquilizer that blocks dopamine receptors and causes sedation with minimal to no effect on anxiety. Dogs may show signs of increased frustration as motor function becomes compromised.20 Sedation can negatively affect social interactions because sedated dogs are less playful and less social.

ALPRAZOLAM

Correct ResponseDo Not UseAlprazolam is a benzodiazepine with an intermediate half-life that can be useful as an event drug for context-specific anxiety. This drug can also be prescribed chronically, typically as an augmenting agent with an SSRI, for patients with severe anxiety or panic. Benzodiazepines have been associated with behavioral disinhibition and are not recommended in patients with redirected aggression.21,22

Discussion

There is no FDA-approved medication for treatment of aggression in dogs. Informed consent should be obtained from the owner prior to administering medication for extra-label use.

Medication should be considered only one part of a behavioral treatment program. Management of environment and behavior modification are necessary for a positive outcome in most cases of intrahousehold interdog aggression. In this case, desensitization and counterconditioning can reduce Betty’s intrahousehold interdog aggression. Response substitution (eg, training Betty to move away on cue in response to an outside trigger) may prevent a physical confrontation with the owner and can be used to treat redirected aggression.

*Most medications in this article are extrapolated from human use unless otherwise specified.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Chronic Enteropathy in Cats

Heather Kvitko-White, DVM, DACVIM (SAIM), KW Veterinary Consulting, Kansas City, Missouri

Internal Medicine

|Peer Reviewed

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Chronic Enteropathy in Cats

Background & Pathophysiology

Chronic enteropathy refers to GI signs of >3 weeks’ duration.1-4 Inflammatory bowel disease (IBD) and small cell lymphoma are the most common causes of chronic enteropathy in cats in which infectious and non-GI causes have been excluded. These diseases also have clinical and histopathologic similarities that can complicate differentiation.2-4 Slow progression of IBD to low-grade lymphoma is suspected but has not been proven.3,5-7

In patients with IBD, the underlying cause of inflammation is multifactorial and incompletely understood; however, there is ongoing research on the role of the microbiome in local immune regulation, GI barrier function, and inflammation.8-14 Metabolites produced by gut microbes help maintain body functions (eg, metabolism, immunity, GI tract motility).8,9 Dysbiosis describes fluctuations in the number of various bacteria and their metabolites; changes in the relative proportions of 7 bacterial targets are characterized by decreased numbers of beneficial bacteria (eg, Bacterioides spp, Bifidobacterium spp, Faecalibacterium spp, Turicibacter spp, Clostridium hiranonis) and increased numbers of pathogenic bacteria (eg, Escherichia coli, Streptococcus spp) and can be measured via quantitative PCR in cats and dogs.1,10,11

History & Clinical Signs

IBD can occur in cats of any age, breed, or sex but is most frequently diagnosed in middle-aged and older cats.1,11-18 Clinical signs are variable; vomiting and weight loss are most common and typically coincide with changes in appetite.15-17 Diarrhea is possible and can be small, large, or mixed bowel. Borborygmi, flatulence, and ascites are less common in cats as compared with dogs.11-15

CAUSES OF GI TRACT INFLAMMATION IN CATS

Inflammatory

  • Feline triaditis (ie, IBD, pancreatitis, ± cholangitis)
  • Dysbiosis
  • Exocrine pancreatic insufficiency 
  • GI eosinophilic sclerosing fibroplasia
  • Chronic intestinal pseudo-obstruction (intestinal leiomyositis)

Infectious

  • Parasitic/protozoal
    • Ancylostoma spp
    • Cryptosporidium spp
    • Giardia spp
    • Toxocara spp
    • Toxoplasma gondii
    • Tritrichomonas foetus
  • Bacterial
    • Salmonella spp
    • Campylobacter spp 
    • Clostridium spp
    • Helicobacter pylori
  • Fungal
    • Histoplasma capsulatum
  • Viral
    • FIV
    • FeLV
    • FIP

Neoplastic

  • Lymphoma (small, intermediate, ± large cell) 
  • Adenocarcinoma
  • Mast cell neoplasia
  • Soft tissue/mesenchymal tumors

Miscellaneous

  • Intestinal foreign body
  • Intestinal obstruction 
  • Acute gastroenteritis (eg, dietary indiscretion, intoxication)
  • Non-GI causes (eg, hyperthyroidism, moderate to severe renal or hepatic disease)

Diagnosis

Fecal ova and parasite testing should be performed to exclude infectious GI inflammation, and additional diagnostics should be performed to rule out non-GI causes of clinical signs (see Differential Causes of GI Tract Inflammation in Cats).

CBC results may be unremarkable or show a nonspecific nonregenerative anemia of chronic disease. Leukogram changes (eg, eosinophilia) are possible.2,15 

Serum chemistry profile results may be unremarkable, have nonspecific changes, or be impacted by comorbidities. Protein-losing enteropathy caused by IBD is rare in cats; however, low blood cholesterol, albumin, and globulins suggest protein loss through GI causes (versus protein-losing nephropathy or hepatic insufficiency). Hypoproteinemia with melena, regenerative blood loss anemia, or iron-deficient nonregenerative anemia with or without increased BUN may suggest GI hemorrhage.

Serum cobalamin and folate levels reflect the absorptive ability of the ileum and proximal small bowel, respectively, and supplementation is indicated when they are deficient.2 Increased folate in a nonsupplemented cat may suggest dysbiosis; the feline dysbiosis index is also a diagnostic test for dysbiosis in cats with chronic enteropathy.1

Trypsin-like immunoreactivity should be evaluated to exclude exocrine pancreatic insufficiency, which is an underrecognized cause of vomiting and anorexia in cats with or without diarrhea.2,18 Many cats with IBD have concurrent pancreatitis with or without cholangitis (ie, triaditis) that may result in elevation of pancreatic lipase immunoreactivity levels.2,15 

Radiography is nonspecific, and radiographs may appear normal. Ultrasonographic findings may include thickening of the general bowel wall or muscularis layer (Figure 1), mucosal changes, and mesenteric lymphadenopathy; however, ultrasonography is not sensitive or specific for IBD, and results may be normal.19,20 

Ultrasound of the duodenum in a cat showing mild generalized muscularis layer thickening (arrow). The corrugated appearance and increased gas within the lumen (dashed arrow) support spastic hypermotility consistent with duodenitis, assuming an upper GI linear foreign body has been excluded.
Ultrasound of the duodenum in a cat showing mild generalized muscularis layer thickening (arrow). The corrugated appearance and increased gas within the lumen (dashed arrow) support spastic hypermotility consistent with duodenitis, assuming an upper GI linear foreign body has been excluded.

FIGURE 1 Ultrasound of the duodenum in a cat showing mild generalized muscularis layer thickening (arrow). The corrugated appearance and increased gas within the lumen (dashed arrow) support spastic hypermotility consistent with duodenitis, assuming an upper GI linear foreign body has been excluded.

FIGURE 1 Ultrasound of the duodenum in a cat showing mild generalized muscularis layer thickening (arrow). The corrugated appearance and increased gas within the lumen (dashed arrow) support spastic hypermotility consistent with duodenitis, assuming an upper GI linear foreign body has been excluded.

Intestinal biopsies are required for definitive diagnosis, to rule out differentials (eg, neoplasia, certain infectious diseases), and to allow further classification of IBD based on cellular infiltration type (eg, eosinophilic, neutrophilic, lymphocytic/plasmacytic).21 Most feline IBD is caused by lymphocytic/plasmacytic and/or eosinophilic inflammation.21 Combining GI biopsies with immunohistochemistry and PCR for antigen receptor rearrangement (ie, PARR) improves the ability to differentiate IBD from lymphoma.3 Biopsies should be obtained through an endoscopic or full-thickness surgical approach (Figure 2). Applying and interpreting clonality testing presents additional clinical challenges; discussion is available in the literature.2-4

Classic belly button appearance of the ileocolic junction during routine colonoscopy. The shiny mucosal lining appears slightly hyperemic and edematous, although these findings can occur secondary to the endoscopy procedure. Partially open entry to the blind sac of the cecum is visible (arrow).
Classic belly button appearance of the ileocolic junction during routine colonoscopy. The shiny mucosal lining appears slightly hyperemic and edematous, although these findings can occur secondary to the endoscopy procedure. Partially open entry to the blind sac of the cecum is visible (arrow).

FIGURE 2 Classic belly button appearance of the ileocolic junction during routine colonoscopy. The shiny mucosal lining appears slightly hyperemic and edematous, although these findings can occur secondary to the endoscopy procedure. Partially open entry to the blind sac of the cecum is visible (arrow).

FIGURE 2 Classic belly button appearance of the ileocolic junction during routine colonoscopy. The shiny mucosal lining appears slightly hyperemic and edematous, although these findings can occur secondary to the endoscopy procedure. Partially open entry to the blind sac of the cecum is visible (arrow).

Treatment & Management

Many differential diagnoses for IBD require specific therapy; it is not feasible to treat empirically for all possibilities. Minimum treatment should include broad-spectrum deworming (fenbendazole, 50 mg/kg PO every 24 hours for 3-5 days). Otherwise, treatment should be tailored to the patient.  

Many cats with IBD can be diet responsive, and a strict 2- to 4-week diet trial is often recommended as initial treatment. There are multiple dietary options (eg, highly digestible, novel protein, hydrolyzed protein, nonallergenic), and evidence supporting a specific diet in affected patients is lacking. Younger cats with predominantly large bowel signs may be an exception; a highly digestible, fiber-modified diet can be attempted first in these patients.  

The author administers cobalamin when the patient has borderline low levels (<400 ng/L). Folate supplementation is rarely required or prioritized. 

Antibiotic administration results in prolonged microbiota changes with potentially harmful effects in dogs and cats.22-24 Routine antibiotic trials and chronic use of low-dose or repeat courses of antibiotics are not recommended. 

Prebiotics, probiotics, or synbiotics (ie, pre- and probiotic combinations) can be administered when diet alone does not control clinical signs; data to provide critical assessment of benefits are lacking.25 A positive response, if any, should be observed in 2 to 4 weeks.  

Immunosuppression should only be considered in stable patients after thorough diagnostic evaluation, failed response to diet and probiotic trials, and pursual or pet owner decline of biopsies. Corticosteroids (eg, prednisolone, budesonide, dexamethasone) or chlorambucil may be administered as first-line options based on numerous factors, including comorbidities, cost, and owner ability to medicate the patient (Table). Sustained improvement with corticosteroids does not exclude a diagnosis of small cell lymphoma.

After stabilization of clinical signs and weight, the immunosuppressive dose should be tapered by ≈25% every 2 to 4 weeks until the lowest effective dose is determined. Some patients can be maintained on diet and/or probiotics alone following drug tapering, but continued treatment with one or more immunosuppressive medications may be required. 

Fecal microbiota transplant has been performed in cats, but large-scale studies are lacking.26 Collaboration with a veterinary nutritionist should be considered. 

Table

IMMUNOSUPPRESSIVE MEDICATIONS FOR CHRONIC ENTEROPATHY IN CATS

Drug Dosage
Budesonide 1 mg/cat PO every 24 hours
Dexamethasone 0.1-0.3 mg/kg SC or IV every 24 hours OR 0.125-0.5 mg/cat PO every 24 hours or divided and given every 12 hours
Prednisolone 1-2 mg/kg PO every 24 hours
Cyclosporine 5-7.5 mg/kg PO every 24 hours on an empty stomach
Chlorambucil 2 mg/cat PO every 48-72 hours  OR 20 mg/m2 PO every 14 days

 

Clinical Follow-Up & Monitoring

Objective markers of successful treatment include weight gain, improved BCS, and improved fecal consistency score; trends are more important than individual values. Monitoring can occur weekly, monthly, biannually, or perhaps annually, depending on initial disease severity. 

Individual patient plans are needed because of comorbidities in middle-aged and older cats. Owner communication should be maintained, and the veterinary support team can help provide owner support through education and communication.

Prognosis

Chronic enteropathy in cats can be managed but not cured. Clinical signs may resolve, decrease, persist, increase, progress, or otherwise change over time. In one study of 62 cats with chronic enteropathy, median survival time in cats with IBD was 5.8 years compared with 1.3 years in cats with small cell lymphoma.27 Standard therapy should help maintain a good quality of life; further investigation or specialist referral is encouraged if quality of life is not maintained.

References

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Differential Diagnosis: Icterus in Cats

Todd Archer, DVM, MS, DACVIM, Mississippi State University

Internal Medicine

|Peer Reviewed

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Differential Diagnosis: Icterus in Cats

Following are differential diagnoses for cats presented with increased icterus.

Prehepatic causes (hemolysis)

  • Immune-mediated hemolytic anemia, primary or secondary
    • Blood transfusion
  • Non-immune–mediated cause
    • Drug-induced
    • Erythrocyte fragmentation (eg, hemangiosarcoma) 
    • Erythrocyte membrane or enzyme defects (hypophosphatemia, pyruvate kinase deficiency) 
    • Infectious disease
    • Paraneoplastic syndrome
    • Toxin exposure (eg, onion, garlic) 

Hepatic causes (hepatocellular dysfunction)

  • Fibrosis
  • Hepatic lipidosis
  • Inflammatory or infectious hepatopathy (hepatitis/cholangiohepatitis)
  • Neoplasia  
  • Toxin or drug hepatopathy

Posthepatic causes (cholestasis, defective biliary excretion)

  • Diseases of the biliary system 
    • Biliary system rupture  
    • Gallbladder disease 
    • Cholelithiasis
    • Stricture
    • Infection (including parasite-induced)
    • Inflammation
    • Neoplasia
  • Diseases outside the hepatobiliary system 
    • Enlarged regional lymph nodes
    • Intestinal disease or obstruction
    • Neoplasia (pancreas, duodenum)
    • Pancreatitis
*Bilirubin can be artifactually increased by lipemia and hemolysis
**Serum bilirubin values >1 mg/dL produce serum icterus; values >2 mg/dL produce tissue jaundice

For global readers, a calculator to convert laboratory values, dosages, and other measurements to SI units can be found here.

All Clinician's Brief content is reviewed for accuracy at the time of publication. Previously published content may not reflect recent developments in research and practice.

Material from Digital Edition may not be reproduced, distributed, or used in whole or in part without prior permission of Educational Concepts, LLC. For questions or inquiries please contact us.


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Clinical Notes: How Cytopoint Paved the Way for Monoclonal Antibody Therapy in Veterinary Medicine

Clinical Notes: How Cytopoint Paved the Way for Monoclonal Antibody Therapy in Veterinary Medicine

Candace A. Sousa, DVM, DABVP (Emeritus, Canine & Feline), DACVD (Emeritus)

Dermatology

|Peer Reviewed|Sponsored

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Clinical Notes: How Cytopoint Paved the Way for Monoclonal Antibody Therapy in Veterinary Medicine
Sponsored by Zoetis 

KEY POINTS

  • Monoclonal antibody (mAb) therapy mimics the body’s natural immune defense processes and works by binding to and neutralizing extracellular targets such as circulating molecules or cellular receptors. mAbs are highly targeted therapeutics and can have distinct advantages over traditional small molecule pharmaceuticals, but understanding the pathophysiology of the disease being treated is key to identifying an effective antibody target.
  • The cytokine IL-31 has been shown to induce pruritus when injected into dogs, and identifying IL-31 as a therapeutic target has led to the development of more targeted medications for the treatment of canine AD, particularly mAbs.
  • Cytopoint® (lokivetmab), a caninized mAb therapy, has been shown to be effective in the treatment of dogs against allergic and atopic dermatitis.
  • Other mAbs that would block canine IL-31 in a different way could potentially be developed for use in animals; however, clinical trials, documented safety, and pharmacovigilance reporting would be needed before a valid, positive comparison of clinical safety or efficacy could be made to Cytopoint.

Monoclonal antibody (mAb) therapy has been available for almost 4 decades to treat a wide range of diseases in human health1 but is a relatively new therapeutic option in veterinary medicine. Cytopoint® (lokivetmab) is a caninized mAb therapy and the first mAb product that has been shown to be effective in the treatment of dogs against allergic and atopic dermatitis. Since the approval of Cytopoint, additional mAb products have been approved in various countries for the treatment of other chronic conditions. Examples include frunevetmab (Solensia®) for the control of osteoarthritis (OA) pain in cats and bedinvetmab (Librela®) for alleviation of OA pain in dogs.

This article outlines the clinical use of mAb therapies for dogs with allergic and atopic dermatitis, developments that may lay ahead, and what clinicians should consider as this area of veterinary medicine continues to expand.

An Introduction to Monoclonal Antibody Therapy

In the 20th century, scientists realized the specific and highly targeted nature of the body’s normal immune response to disease could be applied to the development of a new therapeutic approach.1 Antibodies directed at specific body (or self) proteins involved in a given disease process could be produced outside of the patient, then injected to disrupt a disease process by neutralizing a protein that plays a core role in the pathogenesis of a disease (Figure 1). In 1973, Jerrold Schwaber described the production of mAbs using human–mouse hybrid cells,2 and in 1975, Georges Köhler and César Milstein succeeded in making fusions of myeloma cell lines with B cells to create hybridomas, which could produce antibodies specific to known antigens and that were then immortalized.3

Antibodies bind to a circulating protein to neutralize it.

FIGURE 1 Antibodies bind to a circulating protein to neutralize it.

Treatment with mAbs mimics the body’s natural immune defense processes, wherein antibodies may be generated to neutralize a target such as bacteria or a virus. Traditional small molecule therapeutics (eg, antibiotics, Janus kinase inhibitors, corticosteroids) target sites inside the cell, whereas mAb therapy works by binding to and neutralizing extracellular targets such as circulating molecules or cellular receptors.

mAbs can have distinct advantages over traditional small molecule pharmaceuticals.4 The antibody–target complexes are broken down in the body slowly over time like other proteins via catabolic processes and lysosomal degradation.4 The half-life and correlated duration of the therapeutic effect of an mAb can be long-lasting, as therapeutic mAbs utilize the neonatal Fc receptor antibody recycling mechanism. Unlike traditional drug therapy, catabolism does not rely on the patient’s kidney or liver drug metabolism function, making antibody therapy a treatment consideration for dogs regardless of age, major organ drug-metabolizing capacity, or potential for interference with metabolism of other medications being administered concurrently.4 In addition, residual unbound mAbs in circulation do not cause adverse effects because they are a small part of the pool of antibodies already present in blood for circulating immunity. Once targets are saturated with mAbs, the remaining unbound mAbs do not have an effect anywhere else in the body.4

Developing Monoclonal Antibody Therapies

Unlike many small molecule therapies, mAb therapies are highly targeted therapeutics.4 Understanding the pathophysiology of the disease being treated is key to identifying an effective antibody target. Furthermore, understanding what role the targeted cytokine (or other protein) has in the body is critical to determining the safety of the therapy. If a targeted cytokine has multiple physiologic functions in the body, unwanted effects could occur, resulting in safety concerns or unwanted adverse effects.4

Research on the pathophysiology of canine atopic dermatitis (AD) has identified the major immunologic mediators driving pruritus and inflammation: cytokines, small protein molecules secreted by cells that have a specific effect on the interactions and communications among cells.5 Cytokines fuel an interconnected multidirectional network of biochemical interactions that create the clinical syndrome known as AD, including the disruption of the barrier function, pruritus, inflammation, and the resultant clinical lesions.

Regardless of the underlying and inciting causes, cytokines are one of the common denominators in allergic and atopic skin conditions.

In allergic skin disease, cytokines are primarily released by cells such as T-helper 2 (Th2) lymphocytes, but many cell types that interact with allergens (eg, keratinocytes, dendritic cells, macrophages) can also respond by releasing cytokines.5 They provide communication among the skin, nervous system, and immune system and are the primary cause of the neuronal itch, which is the hallmark of allergic skin disease.5

Regardless of the underlying and inciting causes, cytokines are one of the common denominators in allergic and atopic skin conditions. In dogs with allergic skin disease, multiple cytokine mediators, including interleukin (IL)-2, IL-4, IL-5, IL-6, IL-13, and IL-31, are implicated. Each of these cytokines plays a specific role in the production of clinical signs such as pruritus and skin inflammation (Figure 2).5

Multiple cytokines are released from lymphocytes to coordinate the clinical signs seen in dogs with atopic dermatitis.

FIGURE 2 Multiple cytokines are released from lymphocytes to coordinate the clinical signs seen in dogs with atopic dermatitis.

Interleukin-31

The cytokine IL-31 has been shown to induce pruritus when injected into dogs.6 It has also been found to be significantly increased in the serum of dogs with naturally occurring AD (Table).6-8

IL-31 receptors are found on sensory neurons in the skin, and IL-31 mediates pruritus directly by binding to and activating these neurons. IL-31 also binds directly to IL-31 receptors on other cell types to cause the release of proinflammatory mediators from cells such as keratinocytes and immune cells triggering skin inflammation.

TABLE

SERUM LEVELS OF IL-31 IN VARIOUS CANINE POPULATIONS

Population Median (fg/mL) Arithmetic Mean (fg/mL)
Normal dogs (55) 154 531
Atopic dogs (243) 871 13,541
Crossbreed dogs (no fleas) 273 591
Crossbreed dogs (fleas for 14 days) 1917 2988

 

Identifying IL-31 as a therapeutic target has led to the development of more targeted medications for the treatment of canine AD, particularly mAbs. It became understood that an mAb that inhibits the function of IL-31 could hold the potential to uniquely and specifically improve the signs of allergic dermatitis without the adverse effects associated with broad spectrum pharmacotherapy; this understanding led to the development of Cytopoint.

Pruritus: A Major Pet Owner Concern

Pruritus is the most common reason dog owners present their pet to a veterinarian beyond wellness care.9 There are many conditions that can cause a dog to be pruritic, including parasites, infections, and, commonly, allergic skin disease. Despite how common it is, treatment options for canine AD and its associated pruritus are not always ideal; for example, the International Committee on Allergic Diseases of Animals considers antihistamines to be of little to no benefit in the treatment of acute flares of AD.10 In addition, studies have suggested that 10% to 81% of patients receiving glucocorticoids or cyclosporine may experience adverse effects.11,12

In a survey, when owners were asked about the quality of life of their dogs with allergic and atopic skin disease, ≈90% believed that they understood the disease, and >96% accepted that their dog would require lifelong care.13 Also in this survey, which was conducted prior to FDA approval of Apoquel® (oclacitinib), ≥88% of surveyed dog owners were dissatisfied with the treatment options that were previously available to them, as it was either a major burden or they were unsure about the best therapeutic option.13 In another survey, 36% were also dissatisfied with the treatment options available.14 Thus, a need to develop alternate treatment options for this long-term chronic disease was identified.

The Efficacy of Cytopoint Against Allergic Dermatitis in Dogs

Scientists at Zoetis worked to produce a caninized mAb therapy that would bind to and neutralize soluble IL-31 and could be used as a treatment for AD. This mAb therapy is lokivetmab (Cytopoint). The importance and clinical relevance of targeting IL-31 has been established through the significant improvements reported in allergic pruritus and dermatitis severity in dogs associated with atopic and allergic skin disease following administration of Cytopoint in numerous clinical studies.15-23

Cytopoint has a mean serum half-life of 16 days and therefore remains in circulation for several weeks.15 In the United States, it is labeled to be administered subcutaneously at a minimum dose of 2 mg/kg every 4 to 8 weeks or as needed.24 In Europe, it is labeled to be administered monthly or as needed after a dose of 1 mg/kg.25

In a 2016 clinical trial, Cytopoint was shown to significantly decrease allergic pruritus after 1 day when administered to dogs with AD at 2 mg/kg, with maximal improvement seen by day 7 (Figure 3).15

Cytopoint significantly decreases pruritus after 1 day when administered at 2 mg/kg to dogs with AD, with maximal improvement seen by day 7.

FIGURE 3 Cytopoint significantly decreases pruritus after 1 day when administered at 2 mg/kg to dogs with AD, with maximal improvement seen by day 7.

A significantly greater proportion of dogs receiving Cytopoint at 2 mg/kg achieved treatment success from days 1 to 56 based on owner assessment of pruritus (visual analog scale [VAS]) as compared with placebo.15 Treatment success was defined as at least a 2-cm (20-mm) pruritus score reduction from baseline. This same study showed Cytopoint was effective in reducing initial client VAS scores by at least 50% in 57% of patients at 28 days.15 The clinical trial also demonstrated that the skin condition of these dogs significantly improved within the first week as compared with placebo-treated dogs, as measured by veterinary dermatologists using the Canine Atopic Dermatitis Extent and Severity Index (CADESI-03; Figure 4).15

The skin condition of atopic dogs treated with 2 mg/kg of Cytopoint significantly improved within the first week as compared with placebo-treated dogs, as measured by veterinary dermatologists using the Canine Atopic Dermatitis Extent and Severity Index (CADESI-03).

FIGURE 4 The skin condition of atopic dogs treated with 2 mg/kg of Cytopoint significantly improved within the first week as compared with placebo-treated dogs, as measured by veterinary dermatologists using the Canine Atopic Dermatitis Extent and Severity Index (CADESI-03).

In a retrospective study, 87.8% of dogs with a variety of confirmed allergic dermatoses (eg, AD, adverse food reaction, allergic disease of undetermined cause) treated with Cytopoint were regarded as “successful” using the previously described definition of success.17 Thus, in that study, Cytopoint had demonstrated efficacy not only for dogs with AD but also for dogs with other skin allergies, even when the specific underlying cause of allergic dermatitis was uncertain.18

The Safety of Cytopoint

Cytopoint is safe and effective for dogs of all ages and sizes, those receiving a variety of concomitant medications, and those with comorbidities.15-18,26 Adverse effects reported in the original studies (cited on the US package insert) for dogs that were administered Cytopoint and for the placebeo control group were found to have similar frequency to one another. These adverse effects consisted primarily of minor pain at the injection site.15

During a continuation therapy study, the European Medicines Agency Committee for Medicinal Products for Veterinary Use concluded that there is sufficient safety data to alleviate concerns that chronic use could lead to immunosuppression, an increased need for antibacterial medications, or treatment-induced immunogenicity.27

In another study, the safety of Cytopoint was evaluated, showing it to be well tolerated when administered to laboratory beagles at up to 10 mg/kg for 7 consecutive monthly doses.28 Enhanced pathology evaluations of immune tissue revealed no changes in any lymphoid tissue that would be suggestive of a treatment effect. In addition, no safety concerns regarding immunogenicity of the molecule have been identified. The only treatment-related change in the laboratory- based study was a mild tissue reaction at the injection site and the draining lymph nodes seen on histopathology.28

Cytopoint has changed the quality of life of many of these animals and their owners.

Cytopoint is approved for use in most major companion animal markets, including the United States, the European Union, Australia, and countries in Asia. Since Cytopoint became available to veterinarians in 2016, more than 5.5 million dogs in the United States have been treated.29 The reported adverse effects are generally consistent with those observed in clinical trials.15,16 The most commonly reported adverse events not related to the skin in clinical trials to support global registrations were mild GI signs (vomiting and diarrhea) and lethargy.16,26 Adverse events appear to occur in rates similar to placebo groups.24

Cytopoint has changed the quality of life of many of these animals and their owners.30 When US dog owners were surveyed in 2021, 90% reported that they were either “satisfied” or “very satisfied” with Cytopoint therapy.31 In a global survey, 60% of veterinarians surveyed were “satisfied” or “very satisfied” with Cytopoint therapy.32

The Future of Monoclonal Antibody Therapy

Veterinary researchers are now investigating the role of canine IL-31 in pruritus caused by diseases other than allergies. Some initial studies have found that Cytopoint, while binding only to circulating IL-31, has demonstrated an effect on the clinical signs for several different conditions.33,34 Researchers are also looking at other targets for the development of monoclonal antibodies to treat pruritus and allergic dermatitis in a variety of species.5

Other mAbs that would block canine IL-31 in a different way—either by binding to the IL-31 receptor or to an epitope on the cytokine different than lokivetmab—could potentially be developed for use in animals. Large-scale clinical trials, short- and long-term safety documented in laboratory and clinical trials, and postmarketing pharmacovigilance reporting would be needed before a valid, positive comparison of clinical safety or efficacy could be made to Cytopoint. Even a product with the same cytokine target as Cytopoint could have seemingly minor differences that impact efficacy and therefore the clinical condition. Efficacy of an individual product should not be presumed without supportive data.

Other mAbs that would block canine IL-31 in a different way—either by binding to the IL-31 receptor or to an epitope on the cytokine different than lokivetmab—could potentially be developed for use in animals.

Because veterinary medicine has led the way in targeting IL-31 for the treatment of allergic skin disease in dogs, human medicine researchers are now looking at a similar therapeutic with either a humanized anti–IL-31 mAb therapy or an mAb that targets and blocks the IL-31 receptor. There are ongoing studies evaluating mAbs that target IL-4 and IL-13 receptors to treat AD in humans.35 There are also clinical trials using humanized mAbs that target circulating IL-5, -13, -17, -12/23, -22, and -33 and thymic stromal lymphopoietin.35

In human medicine, biosimilar mAbs are now being approved. Biosimilars are not completely identical to the original product for many reasons; biosimilars are developed to have an analogous area of action as the reference molecule but, for example, may bind to a different epitope or may have different impurity profiles (because the processes used to manufacture the reference molecule are proprietary to the company that registered the original reference molecule).36 A certain amount of molecular variability is unavoidable. Biosimilar mAbs are not the same as generic small molecules, which can be precisely replicated and deemed bioequivalent to the original product. Clinicians should have a clear understanding of how these products can be used and prescribed. From a clinical point of view, some differences have to be carefully considered. Differences in efficacy, immunogenicity, and adverse events are possible and may be pronounced with long-term use. The approval of biosimilars is only partially based on the results of clinical trials.37 To date, there are no biosimilars for the few mAbs available in veterinary medicine.

Although Cytopoint has been shown to be an effective treatment for many dogs with AD and allergic dermatitis, not all dogs respond to it; other cytokines or cytokine receptors may be potential targets. In addition to in vitro studies, clinical trials would be needed to prove the relevance and impact on the clinical condition, as well as the safety of blocking the specific target. As has occurred in human medicine, products that combine more than one mAb may be developed for the treatment of allergic skin disease.

Clinician's Brief

Conclusion

For treatment of a lifelong disease such as canine AD, the development and use of a biologic such as Cytopoint has changed the lives of millions of allergic dogs, their owners, and the veterinarians who treat them. As this area of veterinary medicine continues to evolve, with mAbs developed for the management of other canine and feline diseases, clinicians should stay informed and understand the relevance of the molecular target to the disease they are treating and the potential effects of blocking the target with a biologic therapy. Clinicians should also continue to critically assess the evidence available to support the efficacy and safety for each product used in their practice.

References

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