C

C


Cachexia, Cancer-Associated


AUTHOR: GLENNA E. MAULDIN



EDITOR: KENNETH M. RASSNICK



BASIC INFORMATIONimage



DEFINITION


The term cancer cachexia refers to weight loss in an animal or person with underlying neoplastic disease. Classic defining clinical features of the syndrome include severe involuntary weight loss, fatigue, anemia, and progressive depletion of both lean body mass and adipose stores.



SYNONYM


Cancer-associated weight loss



EPIDEMIOLOGY



SPECIES, AGE, SEX


Cancer cachexia has been reported in association with neoplastic disease in many species, including people, cats, and dogs with naturally occurring malignancies, as well as laboratory rodents bearing implanted tumors. Animals of any age and either sex may be affected.



RISK FACTORS



• Advanced clinical stage of neoplastic disease

• Tumors of the upper gastrointestinal tract (esophagus, stomach, and pancreas) in humans

• Lower risk in people with treatment-responsive lymphomas, soft-tissue sarcomas, and breast cancer

• Cancer cachexia is less common in dogs than in people.

• Cats appear to be at greater risk for cancer cachexia than dogs: up to 90% of cats with neoplastic disease experience clinically apparent loss of lean body mass.


ASSOCIATED CONDITIONS & DISORDERS


Cancer cachexia is a form of protein-energy malnutrition, the most common form of malnutrition found in critically ill animals and people. It occurs when protein and energy intake is insufficient to meet requirements. Protein-energy malnutrition is associated with hypoproteinemia, delayed wound healing, immunosuppression, and compromised gastrointestinal, pulmonary, and cardiovascular function. Multiorgan failure and death will be the eventual outcome unless nutritional support is provided and the primary underlying disease process is resolved.



CLINICAL PRESENTATION



HISTORY, CHIEF COMPLAINT


Although weight loss is the primary abnormality in all cats and dogs with cancer cachexia, specific historical findings differ substantially from animal to animal. Weight loss may be mild to profound in severity, ranging from acute to chronic in duration. Weight loss is also superimposed on any clinical signs associated with the underlying neoplastic disease, which vary with the specific diagnosis.



PHYSICAL EXAM FINDINGS


Physical exam findings in animals with cancer cachexia can be divided into two groups: abnormalities related to cancer cachexia, and abnormalities caused by the animal’s underlying cancer. The clinical signs associated with cancer cachexia are nonspecific, initially may be subtle, and can easily be overlooked. Findings may include muscle wasting, pallor, weakness, poor haircoat, hepatomegaly, splenomegaly, evidence of chronic infections, and lymphadenopathy. Peripheral edema could be present in severe cases. Physical exam findings related to the underlying malignancy are highly variable and depend on the animal’s specific histopathologic diagnosis and stage of disease. No two animals with cancer cachexia have exactly the same presentation.



ETIOLOGY AND PATHOPHYSIOLOGY



• The etiology of cancer cachexia is highly variable and multifactorial.

• There are two major categories of cancer cachexia: primary and secondary.

• Primary cancer cachexia is an incompletely understood paraneoplastic syndrome in which tumor-related changes in host metabolism lead to inefficient use of consumed calories, in turn leading to gradual depletion of lean body mass and adipose stores. No matter how many calories are fed or by what route, host requirements cannot be met.

• Recent studies suggest that primary cancer cachexia may be an inflammatory disorder caused by alterations in proinflammatory mediators such as interleukin (IL)-1 alpha, IL-1 beta, IL-6, tumor necrosis factor alpha (TNF-α), and various eicosanoids.

• Secondary cancer cachexia is caused by one or more of a variety of functional abnormalities that decrease nutrient intake, digestion, or absorption. Examples include the physical presence of tumor within the digestive tract, causing gastrointestinal dysfunction, or side effects of radiotherapy or chemotherapy such as stomatitis, vomiting, and gastroenteritis.


DIAGNOSISimage



DIAGNOSTIC OVERVIEW


Dogs and cats with cancer-associated cachexia have objective evidence of loss of lean body mass and adipose stores as demonstrated by weight loss and a decline in body condition score.



DIFFERENTIAL DIAGNOSIS


Differential diagnoses for weight loss in a cat or dog with cancer:


• Primary cancer cachexia (paraneoplastic abnormalities in energy metabolism)

• Secondary cancer cachexia:
○ Tumor involving the intestinal tract

○ Paraneoplastic syndromes other than cancer cachexia:
▪ Hypercalcemia

▪ Fever

○ Treatment-related toxicity:
▪ Altered taste and smell perception

▪ Learned food aversions

▪ Stomatitis/mucositis

▪ Gastroenteritis

▪ Centrally mediated nausea and vomiting

• Concurrent disease:
○ Infection:
▪ Bacterial, viral, fungal, oomycotic, or rickettsial

○ Organ dysfunction/failure (i.e., liver, kidney, lung)

○ Diabetes mellitus

○ Hyperthyroidism (cats)

• Inappropriate nutritional management (unsuitable diet, inadequate caloric intake)


INITIAL DATABASE



• Diet history (specific ration fed and quantity consumed, plus all treats, supplements, and medications)

• Body weight and body condition score

• CBC

• Serum biochemistry profile

• Urinalysis

• Chest and abdominal radiographs

• Retroviral screening (cats)

• Serum thyroxine concentration (cats)


ADVANCED OR CONFIRMATORY TESTING



• Thoracic and abdominal ultrasonography

• Cross-sectional imaging (CT, MRI)

• Endoscopy

• Urine culture and sensitivity

• Fine-needle aspiration cytology, impression smears, or tissue biopsy to confirm the presence or absence of neoplastic cells, organisms, or other abnormalities in suspected lesions


TREATMENTimage



TREATMENT OVERVIEW


The basic goals of therapy in the cat or dog suffering from cancer cachexia are twofold:


• Return the animal to ideal body condition.

• Maintain the animal in ideal body condition long term.

These goals are accomplished by diagnosing and treating the underlying malignancy and providing appropriate nutritional support.



ACUTE GENERAL TREATMENT



• Cancer cachexia is a paraneoplastic syndrome, so eradication of the underlying neoplastic disease is the best treatment. This goal can be met by:
○ Obtaining a rapid and accurate definitive diagnosis of neoplasia, including neoplasm type and clinical stage

○ Initiating timely and effective antineoplastic therapy

• An individualized feeding protocol is instituted concurrently and is based on the animal’s nutritional assessment as defined by the minimum database outlined previously.


CHRONIC TREATMENT


Nutritional recommendations are adjusted as necessary based on repeat nutritional assessment, with the goal of maintaining ideal body condition:


• Food intake is increased or decreased as needed in response to changes in body weight and condition.

• Assisted feeding can be used intermittently to maintain nutrient intake.

• The specific ration recommended for an individual animal may change depending on the progression of the underlying neoplastic disease and concurrent conditions.


NUTRITION/DIET



• Components of the feeding protocol for an animal with cancer-associated cachexia must include:
○ Fluid requirement in milliliters per day

○ Energy requirement in kilocalories per day

○ A choice of commercial ration that meets the animal’s needs:
▪ Calories appropriately distributed among protein, fat, and carbohydrate

▪ All necessary nutrients (i.e., vitamins and minerals) present in correct quantities and ratios

○ A method of feeding that will be tolerated by the animal

• No single diet is appropriate for every animal with cancer cachexia, because underlying disease, nutritional status, and nutrient requirements are highly variable from case to case.
○ Rations with ample protein and fat are often recommended for weight-losing cats and dogs with cancer.

○ Individual restriction of protein, fat, or carbohydrate intake may be indicated, depending on preexisting or concurrent conditions such as renal or hepatic insufficiency, pancreatitis, or diabetes mellitus.

• Voluntary intake is the most practical feeding technique, but quantities of food and water consumed must be measured to ensure that requirements are actually met.

• Assisted feeding should be instituted without delay in animals unable to meet their own nutrient requirements.

• Assisted enteral feeding using some type of feeding tube is usually preferred, because it allows nutrients to be metabolized through normal pathways and is more effective in maintaining gut health.

• Fluid deficits and electrolyte or acid-base imbalances should be corrected before any type of assisted feeding is attempted.


POSSIBLE COMPLICATIONS



• Gastrointestinal intolerance

• See online chapter: Refeeding Syndrome


RECOMMENDED MONITORING



• Nutritional assessment, including diet history, body weight, and body condition score, should be repeated at regular intervals.

• Diagnostics are repeated as indicated based on underlying neoplastic disease and nutritional status; this commonly includes CBC, serum biochemistry profile, urinalysis, and imaging studies.


PROGNOSIS AND OUTCOMEimage



• Cancer cachexia has a well-documented negative effect on quality of life and prognosis in people, and its impact is highly likely to be the same in cats and dogs.

• Increased incidence and severity of treatment-related toxicities, lower treatment response rates, shorter remission durations, and shorter survival times should be expected in weight-losing animals when compared to weight-stable animals with the same tumor.


PEARLS & CONSIDERATIONSimage



COMMENTS



• Several studies now show that many dogs with cancer are actually obese. Indiscriminate use of high-fat diets in these animals will simply promote additional weight gain and its associated health problems. The primary goal of nutritional therapy in any cat or dog with cancer is always to maintain ideal body weight and condition.

• Recent work suggests that cats with cancer are more likely to have weight loss than dogs. However, it is not yet clear if this weight loss is specifically related to the presence of underlying neoplastic disease, or if it is a generic response to critical illness in the cat.


SUGGESTED READING



Baez JL, Michel KE, Sorenmo K, et al. A prospective investigation of the prevalence and prognostic significance of weight loss and changes in body condition in feline cancer patients. J Feline Med Surg. 2007;9:411.


Mauldin GE. Nutritional management of the cancer patient. In: Withrow SJ, Vail DM, editors. Withrow and MacEwen’s small animal clinical oncology. ed 4. St Louis: Saunders Elsevier; 2007:307-326.


Mauldin GE, Davidson JR. Nutritional support of hospitalized cats and dogs. In: Slatter D, editor. Textbook of small animal surgery. ed 3. Philadelphia: WB Saunders; 2003:87-113.


Weeth LP, Fascetti AJ, Kass PH, et al. Prevalence of obese dogs in a population of dogs with cancer. Am J Vet Res. 2007;68:389.




Cachexia, Cardiac



AUTHOR: LISA M. FREEMAN



EDITOR: KATHRYN E. MICHEL



BASIC INFORMATION image



DEFINITION


Weight and lean tissue loss commonly associated with congestive heart failure (CHF)



EPIDEMIOLOGY



SPECIES, AGE, SEX


More common in dogs than in cats



RISK FACTORS


More common in right-sided or biventricular than in isolated left-sided CHF but can occur regardless of underlying cause



ASSOCIATED CONDITIONS & DISORDERS


Occurs secondary to CHF



CLINICAL PRESENTATION



DISEASE FORMS/SUBTYPES


Cachexia ranges in severity from subtle muscle loss to severe, end-stage muscle wasting.



HISTORY, CHIEF COMPLAINT


Heart failure (see p. 470)



PHYSICAL EXAM FINDINGS



• Loss of lean body mass first noted in epaxial, gluteal, scapular, or temporal muscles; may be subtle initially

• Carefully palpate obese animals and animals with ascites or subcutaneous edema to determine whether muscle loss is present.


ETIOLOGY AND PATHOPHYSIOLOGY



• Cardiac cachexia reduces strength, immune function, and survival.

• Decreased food intake, increased energy requirements, and production of the inflammatory cytokines, tumor necrosis factor (TNF) and interleukin 1 (IL-1)
○ TNF and IL-1 cause anorexia, increased energy requirements, catabolism of lean body mass, myocardial fibrosis, and decreased cardiac contractility (negative inotropy).


DIAGNOSIS image



DIAGNOSTIC OVERVIEW


All animals with CHF should be assessed carefully for early signs of muscle loss so that cachexia can be detected at its early stages when intervention is more likely to be successful.



DIFFERENTIAL DIAGNOSIS


Cachexia from other diseases (e.g., cancer, renal failure)



INITIAL DATABASE



• Diet history, including specific types and amounts of food eaten, dietary supplements, treats, and foods used for administering medications

• Evaluation for potential causes of anorexia (e.g., worsening CHF; medication side effects such as azotemia, hyperkalemia, or hypotension; unpalatable diet)


TREATMENT image



TREATMENT OVERVIEW


The goals of treating cardiac cachexia are to (1) optimally manage CHF, (2) minimize anorexia, (3) reduce energy requirements, (4) ensure adequate protein intake, and (5) modulate cytokine production.



ACUTE GENERAL TREATMENT



• In acute CHF episodes, avoid diet changes until the patient is home and stabilized on medications.

• To avoid food aversions, introduce new diet gradually when patient is stabilized.


CHRONIC TREATMENT



• Ensure optimal medical therapy for CHF (see p. 470).

• Nutritional management is key to the effective chronic treatment of cardiac cachexia (see below).


NUTRITION/DIET



• Tips to minimize anorexia (see p.1377):
○ Reduced sodium diet palatable to individual patient may require diet changes (e.g., dry to canned, or different brand or flavor).

○ Balanced homemade diet formulated by veterinary nutritionist

○ Smaller, more frequent meals

○ Palatability enhancers (cooked meat or low-sodium broth)

○ Fish oil supplementation (see “Modulate cytokine production” below)

• Reduce energy requirements:
○ Optimal management of CHF

○ Exercise restriction

• Ensure adequate protein intake:
○ Avoid protein-restricted diets (e.g., “renal” diets or cardiac diets with <5.1 g/100 kcal protein)

• Modulate cytokine production:
○ Administer one 1-gram fish oil capsule (containing 180 mg eicosapentaenoic acid and 120 mg docosahexaenoic acid) per 5 kg body weight q 24 h.

○ Fish oil should contain vitamin E as an antioxidant, but no other nutrients.

○ Cod liver oil and flaxseed oil should not be used (ineffective).


DRUG INTERACTIONS


Medication side effects can contribute to cachexia by causing anorexia (e.g., digoxin toxicity, azotemia secondary to angiotensin-converting enzyme inhibitor or overzealous diuretic use).



RECOMMENDED MONITORING



• Body weight (be sure to adjust for ascites) and assessment of muscle loss

• Appetite and food intake


PROGNOSIS AND OUTCOME image


Prognosis depends on the underlying cardiac disease. However, anorexia is a common contributing factor to an owner’s decision for euthanasia.



PEARLS & CONSIDERATIONS image



COMMENTS



• Animals with CHF often have variable and cyclical appetites. Reassure owners that this is common, and that they can offer favorite (low-sodium) foods when this occurs. However, anorexia longer than 24-48 hours should trigger reevaluation of CHF and medications.

• Centesis should be performed on anorectic animals with a significant ascites or pleural effusion to reduce fluid accumulation (for comfort).

• Animals with CHF may prefer foods at a particular temperature (e.g., room temperature, warmed, refrigerated, or even frozen).

• Dogs with CHF often prefer sweet tastes, particularly as the disease progresses. Adding items such as maple syrup, fruit-flavored yogurt, or applesauce to the dog’s food may improve food intake.


PREVENTION



• None known

• Early detection in more subtle stages

• Minimize by ensuring adequate food intake and optimal therapy for CHF


CLIENT EDUCATION



• Sodium intake:
○ Provide owner-specific instructions regarding foods high in sodium (to be avoided), appropriate dog foods, acceptable low-salt treats, and methods for administering medications.

• Appetite:
○ Provide the owner with suggestions for improving the animal’s appetite (see Nutrition/Diet above and p. 1377).


SUGGESTED READING



Freeman LM. Nutritional management of heart disease. In: Bonagura JD, Twedt DC, editors. Current veterinary therapy XIV. St Louis: Elsevier; 2009:704-708.


Freeman LM, et al. Nutritional alterations and the effect of fish oil supplementation in dogs with heart failure. J Vet Intern Med. 1998;12:440-448.


Slupe JL, Freeman LM, Rush JE. The relationship between body weight, body condition, and survival in dogs with heart failure. J Vet Intern Med. 2008;22:561-565.



Calcinosis Cutis and Calcinosis Circumscripta



AUTHOR: JOCELYN. WELLINGTON



EDITOR: MANON. PARADIS



BASIC INFORMATIONimage



DEFINITION



• Calcinosis cutis is uncommon and characterized by inappropriate deposition of calcium within the skin. Calcinosis cutis typically denotes a specific form of dystrophic calcification associated with spontaneous or iatrogenic hyperadrenocorticism.

• Calcinosis circumscripta is a localized nodular deposition of calcium in subcutaneous tissue or in other areas such as the tongue, tendons, and ligaments.


EPIDEMIOLOGY



SPECIES, AGE, SEX



• Calcinosis cutis develops as a result of another underlying disorder in dogs, most commonly spontaneous or iatrogenic hyperadrenocorticism. It has been reported in three dogs being treated for blastomycosis with amphotericin B, one dog with atypical fungal infection, and another dog with suspected leptospirosis.

• Calcinosis circumscripta is an uncommon disorder found in dogs younger than age 2 years. It is rare in cats.


GENETICS & BREED PREDISPOSITION


Calcinosis circumscripta is typically found in large-breed dogs, with German shepherds being predisposed.



RISK FACTORS



• Increased risk of calcinosis cutis with chronic administration of exogenous corticosteroids

• Calcinosis circumscripta lesions develop at sites of repetitive trauma.


ASSOCIATED CONDITIONS & DISORDERS



• Calcinosis cutis: hypertrophic osteodystrophy and idiopathic polyarthritis


CLINICAL PRESENTATION



DISEASE FORMS/SUBTYPES


Calcinosis cutis is classified as dystrophic, metastatic, idiopathic or iatrogenic.


• Dystrophic calcification is either localized or generalized. Localized dystrophic calcification occurs as a result of tissue abnormalities or injury. Generalized dystrophic calcification most commonly occurs in dogs with spontaneous or iatrogenic hyperadrenocorticism.

• Metastatic calcification is the calcification of normal skin secondary to an underlying abnormality in calcium or phosphorus metabolism. Although rare, canine and feline metastatic calcification has been reported with chronic renal failure and is restricted to the footpads.

• Idiopathic calcification occurs in localized (calcinosis circumscripta) or generalized forms. The underlying cause is unknown.

• Iatrogenic calcinosis cutis occurs secondary to percutaneous absorption or penetration of calcium-containing products (e.g., calcium chloride). It has been reported in both dogs and cats as a consequence of subcutaneous injections of calcium-containing solution.


HISTORY, CHIEF COMPLAINT



• Dogs affected with calcinosis cutis may present for evaluation of erythematous papules or plaques with gritty surfaces, with or without concurrent pruritus.

• In calcinosis circumscripta, dogs present with a solitary mass over bony prominences or in the oral cavity, particularly the tongue.


PHYSICAL EXAM FINDINGS



• Calcinosis cutis lesions may be found anywhere on the body but typically develop along the dorsum of the trunk, inguinal region, and axillae. Early lesions are erythematous papules that coalesce to form firm, gritty plaques. A chalky white to pink material can be seen through intact epidermis of early nonulcerated lesions. Ulceration and crusting occur during transepidermal elimination of mineralized debris. Lesions can be quite pruritic, leading to extreme self-trauma.

• Calcinosis circumscripta is usually a solitary lesion, but multiple masses are possible. The lesion is a firm, haired to alopecic, well-circumscribed, subcutaneous or deep dermal mass that may ulcerate and discharge a chalky or gritty substance.


ETIOLOGY AND PATHOPHYSIOLOGY



• The pathogenesis of calcinosis cutis and calcinosis circumscripta probably involves abnormally high mitochondrial calcium phosphate levels, resulting in crystal formation and cell death. Calcium salts are deposited along collagen and elastin fibers.


DIAGNOSISimage



DIAGNOSTIC OVERVIEW


Physical examination is the cornerstone of diagnosis: calcinosis cutis is suspected when erythematous papules or plaques that may exude a gritty white substance develop in dogs with iatrogenic or spontaneous hyperadrenocorticism. Biopsies are usually performed for confirmation.



DIFFERENTIAL DIAGNOSIS



• Calcinosis cutis: bacterial pyoderma, deep fungal infection, demodicosis, neoplasia

• Calcinosis circumscripta: neoplasia, foreign body


image EARLY LESIONS OF CALCINOSIS CUTIS. Note the crusted, erythematous papules.

(Courtesy Dr. J. Wellington.)



image CALCINOSIS CUTIS Calcinosis cutis on dorsal cervical region of a boxer with spontaneous hyperadrenocorticism.

(Courtesy Dr. J. Wellington.)



INITIAL DATABASE



• Cytologic evaluation of exudates: amorphous gritty material

• Skin scrapings: sample has gritty consistency when smeared onto microscope slide

• Routine hematologic and biochemical profile: changes associated with hypercortisolism are usually noted in spontaneous and iatrogenic hyperadrenocorticism cases

• Normal calcium and phosphorus levels are typically found, except in patients with metastatic calcification.


ADVANCED OR CONFIRMATORY TESTING



• Skin punch biopsies and histopathologic analysis: multifocal accumulations of finely or coarsely granular amorphous basophilic debris in deep dermal or subcutaneous tissue encompassed by granulomatous inflammation

• Radiographs: conglomerated calcified mass in skin or subcutis with calcinosis circumscripta


TREATMENTimage



TREATMENT OVERVIEW


In most patients with calcinosis cutis, lesions slowly resolve spontaneously once the underlying disease is controlled or resolved. Surgical excision is curative for solitary lesions of calcinosis circumscripta.



ACUTE GENERAL TREATMENT



• Discontinue or reduce dosage of systemic corticosteroids.

• Oral antihistamines and bathing with oatmeal-based shampoo may be effective in controlling pruritus associated with calcinosis cutis.


CHRONIC TREATMENT



• Topical dimethyl sulfoxide applied to up to one-third of body each treatment may dissolve the calcium. If lesions are extensive, serum calcium levels should be monitored for hypercalcemia with this therapy.

• Hydrotherapy and frequent bathing with antibacterial shampoo will reduce pruritus and potential for secondary bacterial infection.


PROGNOSIS AND OUTCOMEimage



• Calcinosis cutis may regress spontaneously without treatment over weeks to months, with resolution or control of the underlying disease.

• Recurrence of calcinosis circumscripta lesions post surgical excision does not occur.


PEARLS & CONSIDERATIONSimage



COMMENTS


In patients with calcinosis cutis associated with excessive glucocorticoids, lesions increase in size, or new lesions may appear for up to 3 months after discontinuing the steroid or treatment of spontaneous hyperadrenocorticism.



SUGGESTED READING



Gortel K, McKiernan BC. Calcinosis cutis associated with systemic blastomycosis in three dogs. JAAHA. 1999;35:368.


Scott DW, Miller WHJr, Griffin CE, editors. Mueller & Kirk’s small animal dermatology. 2001. WB Saunders. Philadelphia. 1398-1401.



Calcipotriene/Vitamin D3 Analog Toxicosis



AUTHOR: MARY. SCHELL



EDITOR SAFDAR. KHAN



BASIC INFORMATION image



DEFINITION


Synthetic vitamin D3 analogs are used topically for treating psoriasis in human and occasionally for treating some skin conditions in dogs and cats. Toxicosis manifests acutely with nonspecific signs of illness and within days may cause kidney disease/renal failure.



SYNONYMS


Calcipotriene, calcipotriol = 1,25 dihydrocholecalciferol (= calcitriol) analog; Tacalcitol = 1,24 dihydrocholecalciferol analog; vitamin D2 = ergocalciferol; vitamin D3 = cholecalciferol. Popular brands (calcipotriene): Dovonex; Taclonex, Dovobet (calcipotriene 0.005% or 50 mcg/g)



EPIDEMIOLOGY



SPECIES, AGE, SEX


Dogs appear to be very sensitive to toxicosis



RISK FACTORS



• Dogs, especially young dogs, with indiscriminate eating habits

• Patients with chronic kidney disease may be at higher risk for adverse renal effects

• Presence of vitamin D3 analog in pet’s environment


CLINICAL PRESENTATION



HISTORY, CHIEF COMPLAINT



• History of ingestion of vitamin D3 analog (chewed up tube/capsules) possible

• Anorexia, vomiting, lethargy, diarrhea within 12-24 hours of ingestion

• PU/PD (due to renal failure) within24-72 hours


PHYSICAL EXAM FINDINGS



• Depression, lethargy, and weakness

• Vomiting (hematemesis), diarrhea (melena)

• Signs of dehydration

• Cardiac arrhythmias

• Seizures (usually seen within 1-3 days of ingestion, if at all)


ETIOLOGY AND PATHOPHYSIOLOGY


Source:


• Vitamin D3 analogs are available by prescription as creams, lotions, ointment, and capsules. Toxicosis occurs secondary to acute accidental ingestions by the patient.

Mechanism of Toxicosis:


• Through calcium-binding proteins, vitamin D3 analogs increase the amount of calcium absorbed from the intestines, as well as increasing bone resorption of calcium and renal tubular resorption of calcium.

• The result is hypercalcemia and hyperphosphatemia.

• Unregulated increases in calcium and phosphorus result in soft-tissue mineralization, especially kidneys, myocardium, large blood vessels, and GI tract.


DIAGNOSIS image



DIAGNOSTIC OVERVIEW


Diagnosis is based on suspected or confirmed history of exposure to calcipotriene or other vitamin D3 analogs and development of clinical signs including vomiting, anorexia, weakness, and lethargy initially; polydipsia, polyuria, and renal failure >24-72 hours after exposure. Hypercalcemia and hyperphosphatemia are noted in virtually all clinically important cases at first and may normalize while renal values rise (renal damage is due to precipitation of calcium in kidneys, and in certain cases, serum calcium and phosphorus levels may have normalized while azotemia persists), indicating renal failure. A patient with normal serum Ca, P, and renal values 3 or more days after exposure either was not exposed or received a minor exposure.



DIFFERENTIAL DIAGNOSIS



• Rodenticide cholecalciferol ingestion

• Other causes for hypercalcemia (see pp. 553 and 1397) plus hyperphosphatemia include chronic kidney disease, hypoadrenocorticism, lymphoma, perianal adenocarcinoma, multiple myeloma, osteolytic tumors.


INITIAL DATABASE



• CBC and serum biochemical profile (hyperphosphatemia and/or hypercalcemia usually in 12 hours; increased BUN, creatinine within 1-3 days if at all; monitor at least every 24 hours for 3-4 days or longer if abnormalities noted.

• Calcium (mg/dL) phosphorus (mg/dL) product (historically, >70 has suggested greater risk for dystrophic mineralization)

• Urinalysis including specific gravity

• Abdominal and thoracic radiographs +/− ultrasound (dystrophic mineralization)


ADVANCED OR CONFIRMATORY TESTING


Rarely practical during active management of toxicosis



• Increased serum 25-hydroxycholecal-ciferol; no assays available to detect calcipotriene in clinical cases

• Total wet weight calcium may be elevated in kidneys.

• Histopathologic evidence of tissue mineralization (kidneys, aorta, GI mucosa, lungs, heart)


TREATMENT image



TREATMENT OVERVIEW



• Immediate treatment of renal failure, cardiac arrhythmias, and seizures as needed

• Prevention of absorption by inducing emesis and administering activated charcoal in promptly presented patient (no clinical signs)

• Promote calciuresis and limit calcium and phosphorus absorption from intestine.

• Inhibit release of calcium and phosphorus from bone.

• Judicious supportive care, notably with intravenous fluids


ACUTE GENERAL TREATMENT



• Prevent absorption: emesis if <4 hours (hydrogen peroxide 3%, 0.25-0.5 mL/kg PO once [dogs] or xylazine hydrochloride, 0.44 mg/kg IM [cats] followed by activated charcoal, 2 g/kg suspended in 10 mL tap water PO; follow label directions for brands) and a cathartic, given q 8 h 24 hours

• Promote calciuresis: saline diuresis using isotonic crystalloids (e.g., 0.9% saline) at 130 mL/kg/d barring cardiovascular contraindications; furosemide, 2.5-4.5 mg/kg PO, IM, or IV q 6-8 h; prednisolone, 1-3 mg/kg PO q 8-12 h

• Inhibit release of calcium and phosphorus from bone (specific antagonist): pamidronate, 1.3-2 mg/kg IV infusion over 2 hours. Repeat in 3-7 days if needed based on persistent hypercalcemia.

• Phosphate binders (e.g., aluminum hydroxide, 10-30 mg/kg PO q 8 h)


CHRONIC TREATMENT


Several days or even weeks of ongoing treatment (including hospitalization) may be needed for treating hypercalcemia, hyperphosphatemia, and renal failure in some cases.



NUTRITION/DIET


Kidney disease dietary therapy (optimized protein, low calcium diet)



POSSIBLE COMPLICATIONS


Calcification of soft tissues—especially in kidneys, lungs, walls of great vessels



RECOMMENDED MONITORING


Follow serum renal, calcium, phosphorus values—initially daily, then weekly until they remain normal without medical support.



PROGNOSIS AND OUTCOME image



• Good if treatment is initiated before persistent hypercalcemia, azotemia, and soft-tissue calcification

• Guarded for several months after a patient recovers from hypercalcemia and hyperphosphatemia of several months’ duration; calcified plaques in walls of great vessels are intrinsically weaker, can rupture


PEARLS & CONSIDERATIONS image



COMMENTS



• Ingestion of 40-60 mcg/kg of calcipotriene or more in dogs can lead to marked hypercalcemia, hyperphosphatemia, renal failure and death.

• Several human supplements contain large amounts of vitamin D, up to 5000 IU (= 0.125 mg).

• 40 IU of vitamin D = 1 mcg or 1 IU of vitamin D3 = 0.025 mcg of cholecalciferol

• The recommended dose of calcitriol for treatment of renal secondary hyperparathyroidism in dogs is 1.65-3.63 ng/kg (please note it is nanogram not microgram) PO q 24 h. This corresponds to 0.00165-0.00363 micrograms per kilogram.


PREVENTION



• Prevent pet access to vitamin D3-containing products.

• Store medications in pet-proof cabinets.


TECHNICIAN TIPS


Keep in mind that topical creams/ointments may be potent (contain vitamin D analogs) and can cause life-threatening intoxications. If an owner is using a human skin cream on a pet’s skin abrasion, be sure the cream does not contain calcipotriene or other similar compound.



CLIENT EDUCATION



• Maintain information on types of topical medications used in the home.

• Keep a list of all medications in the home, separate from the medications themselves.


SUGGESTED READING



Pesillo AS, Khan SA, Rozanski EA, Rush JE. Calcipotriene toxicosis in a dog successfully treated with pamidronate disodium. J Vet Emerg Crit Care. 2002;12(3):177-181.


Rumbeiha WK. Cholecalciferol. In: Peterson ME, Talcott PA, editors. Small animal toxicology. ed 2. St Louis: Elsevier Saunders; 2006:629-642.



Calcium Channel Blocker Drug Toxicosis



AUTHOR: CRISTINE. HAYES



EDITOR SAFDAR. KHAN



BASIC INFORMATION image



DEFINITION


Calcium channel blocker (CCB) drugs are commonly used for the treatment of hypertension and tachyarrhythmias in human and veterinary medicine. Adverse effects at therapeutic dose or with overdose result in hypotension and bradycardia or tachycardia, causing weakness, ataxia, and inappetence within 30 minutes to 12 hours after ingestion.



EPIDEMIOLOGY



SPECIES, AGE, SEX


Animals of all breeds, ages, and both sexes are susceptible. Exposure is more common in dogs.



RISK FACTORS



• Preexisting renal or cardiovascular disease may predispose to signs.

• Hepatic disease may reduce metabolism and elimination of CCBs.


CLINICAL PRESENTATION



DISEASE FORMS/SUBTYPES


Sustained/controlled/extended/delayed-release preparations may delay onset of signs (6-12 hours), whereas immediate-release preparations can cause signs within 30 minutes.



HISTORY, CHIEF COMPLAINT



• History of suspected or observed exposure

• Weakness, depression, ataxia, vomiting possible


PHYSICAL EXAM FINDINGS



• Hypotension and bradycardia are common; reflex tachycardia is possible if hypotension predominates (dihydropyridine CCBs).

• Pale mucous membranes

• Hypothermia possible (due to hypotension)

• Depression, ataxia, seizures, or coma possible

• Dyspnea possible (pulmonary edema)


ETIOLOGY AND PATHOPHYSIOLOGY


Source:


• Prescription medication (human or veterinary)

• Dihydropyridine-type CCBs (e.g., amlodipine [Norvasc]) have effects that are confined to vascular smooth muscle. Thus they are used for treating hypertension.

• Nondihydropyridine-type CCBs (benzothiazepines such as diltiazem [Dilacor, Cardizem] or phenylalkylamines such as verapamil [Isoptin, Calan]) have greater potency in cardiac muscle and cardiac nodal tissues than in the vasculature. Thus they are used for treating arrhythmias and cardiomyopathy.

Mechanism of Toxicosis:


• CCBs close L-type calcium channels by binding to their α-subunit. Decreased calcium influx results in vasodilation (dihydropyridine-type) or a decrease in cardiac contractility and electrical impulse conduction at the SA and AV nodes (nondihydropyridine-type).

• CCBs decrease pancreatic insulin secretion, resulting in hyperglycemia.

• CCBs may cause noncardiogenic pulmonary edema (mechanism unknown)


DIAGNOSIS image



DIAGNOSTIC OVERVIEW


The diagnosis is suspected based on observation or evidence of ingestion (chewed container) along with physical exam findings of hypotension and/or bradycardia. Confirmation with plasma drug levels is uncommonly performed, and treatment generally should be initiated without such results.



DIFFERENTIAL DIAGNOSIS



• Toxicologic:
○ β-Adrenergic receptor antagonists overdose (propranolol, metoprolol), α2-adrenergic receptor agonists (imidazoline-type decongestants), cardiac glycosides (example: digoxin, some cardiac glycoside containing plants; bufo toad toxicosis), antidepressant toxicosis, organophosphate and carbamate insecticides

• Spontaneous, nontoxicologic:
○ Primary cardiac disease, systemic illness causing hypotension


INITIAL DATABASE



• Blood pressure (see p. 1209): hypotension

• Electrocardiogram (ECG; see p. 1253):
○ Sinus bradycardia, AV block with verapamil or diltiazem

○ Sinus tachycardia with dihydropyridines

• Serum chemistry profile: hyperglycemia, hypokalemia, hypophosphatemia, hypomagnesemia possible

• Acid-base status: lactic acidosis possible


ADVANCED OR CONFIRMATORY TESTING


Plasma CCB levels may be measured at a human hospital for confirmation. Therapeutic monitoring to assess response to treatment is not useful, as reference ranges have not been established for animal.



TREATMENT image



TREATMENT OVERVIEW


Treatment consists of decontamination (emesis and charcoal administration), stabilizing the cardiovascular system, and maintaining tissue perfusion by maintaining adequate blood pressure during the course of toxicosis. If no clinical signs are present, continuous monitoring in a veterinary facility for 12-24 hours or longer following ingestion is recommended; signs can be delayed, especially with extended release formulations.



ACUTE GENERAL TREATMENT



• Decontamination
○ Emesis with a recent ingestion or in an animal showing no overt signs of toxicosis (see p. 1364)

○ Activated charcoal: 1-2 g/kg (or labeled dosage) with a cathartic PO following emesis (if performed); repeat half the original dose q 6 h for large ingestions or extended-release preparations.

○ Gastric lavage: if large number of tablets, which can form concretions

○ Enema (see p. 1258): consider if the medication is an extended-release preparation, as significant absorption can occur in colon; 2.5-5 mL/kg of warm tap water or isotonic saline

• Fluid therapy
○ Fluid rate should be guided by blood pressure monitoring; avoid volume overload (iatrogenic pulmonary edema).

• Treatment of hypotension
○ IV crystalloid fluids

○ Hetastarch for persistent hypotension
▪ Dogs: 20 mL/kg/d IV; initial 5 mL/kg bolus over 15-30 minutes, followed by CRI of 15 mL/kg/day

▪ Cats: 10 mL/kg/d IV

○ Calcium chloride or calcium gluconate for refractory hypotension; monitor continuous ECG, and discontinue if bradycardia worsens.
▪ Calcium chloride provides 3 times more calcium per mL than calcium gluconate.

▪ Calcium chloride and calcium gluconate are very irritating and can cause tissue necrosis if extravascular; use indwelling catheter.

▪ Calcium chloride (10% solution; 27.2 mg Ca/mL): 0.1-0.5 mL/kg slow IV bolus or CRI of 0.01 mL/kg/h (5 mg/kg/h), or

▪ Calcium gluconate (10% solution; 9.3 mg Ca/mL): 50-150 mg/kg (0.5-1.5 mL/kg) slow IV over 5 minutes to effect or CRI of 5 mg/kg/h (0.05 mL/kg/h).

○ If hypotension persists after crystalloids, hetastarch, and calcium supplementation, dopamine (1-20 mcg/kg/min IV CRI) may be used, provided the patient is volume-expanded/well hydrated.

• Severe bradycardia/AV block:
○ Atropine: 0.02-0.04 mg/kg IV, SQ, or IM; repeat as needed; or

○ Isoproterenol: 0.4 mg in 250 mL of D5W, drip slowly IV to effect; or

○ Temporary cardiac pacing (see p. 1320)

• Control seizures (see p. 1009) with diazepam (0.5-1 mg/kg IV) or pentobarbital (3-15 mg/kg IV slowly to effect).

• Supplement potassium in hypokalemic patients when the potassium is below 2.5 mEq/L.

• Oxygen therapy if pulmonary edema occurs


CHRONIC TREATMENT


Some animals may need continued treatment for renal insufficiency.



DRUG INTERACTIONS



• CCBs will increase blood levels of propranolol and digoxin.

• Propranolol, ketoconazole, and itraconazole increase CCB levels by reducing clearance of CCBs.

• Cimetidine will increase bioavailability of CCBs.

• Phenobarbital will increase clearance of CCBs.


POSSIBLE COMPLICATIONS



• Pulmonary edema

• Renal insufficiency due to decreased renal perfusion


RECOMMENDED MONITORING



• Blood pressure

• ECG

• Electrolytes

• Serum chemistry panel, especially renal parameters

• Respiration (rate, lung sounds, pulse oximetry)

• CNS signs


PROGNOSIS AND OUTCOME image



• Prognosis is generally good with prompt treatment. Refractory hypotension, severe hyperglycemia, and pulmonary edema may convey a guarded prognosis.

• After recovery, long-term effects are uncommon. Organ dysfunction secondary to sustained hypotension is possible, such as myocardial ischemia or renal failure.


PEARLS & CONSIDERATIONS image



COMMENTS



• Many preparations of CCBs are sustained-, controlled-, extended-, or delayed-release medications, which may substantially lengthen the onset and duration of signs.

• Bezoar formation is possible with ingestion of large quantities of sustained/controlled/extended/delayed-release preparations, especially nifedipine.

• Signs of toxicosis can occur at veterinary therapeutic doses of CCBs. These medications have a narrow margin of safety.

• Noncardiogenic pulmonary edema is possible as a toxic effect; fluid overload should be avoided.


PREVENTION


Owners should keep all medications out of reach of pets.



TECHNICIAN TIPS


It is important to know whether CCB involved in the intoxication is regular or extended-release medication.



CLIENT EDUCATION


Owners should be made aware of possible adverse effects when veterinary patients are prescribed CCBs.



SUGGESTED READING



Costello M, Syring RS. Calcium channel blocker toxicity. J Vet Emerg Crit Care. 2008;18:54.



Calicivirus, Cat image



AUTHOR: CHRISTINE L. WILFORD



EDITOR RANCE K. SELLON



BASIC INFORMATION image



DEFINITION


Common viral disease in domestic and some exotic cats, characterized by upper respiratory signs, oral ulceration, and less commonly arthritis



SYNONYMS


Upper respiratory infection (calicivirus is one possible etiology); limping kitten syndrome; older literature: classification as picornavirus. Virulent systemic feline calicivirus (VS-FCV) is also known as hemorrhagic fever–like FCV



EPIDEMIOLOGY



SPECIES, AGE, SEX



• All domestic cats and some exotic feline species are susceptible.

• All ages affected, but susceptibility for typical upper respiratory infection is highest in kittens.

• Adults are more likely to experience the virulent systemic form of infection.

• No gender predilection


RISK FACTORS



• Multiple-cat environments

• Crowding

• Stress

• Poor husbandry

• Coinfection with other respiratory pathogens worsens disease


CONTAGION & ZOONOSIS


FCV is a highly contagious disease of cats. No zoonotic implications are known.



GEOGRAPHY AND SEASONALITY


Worldwide with no seasonality



ASSOCIATED CONDITIONS & DISORDERS



• Lymphocytic-plasmacytic stomatitis and gingivitis linked to chronic carriers

• Frequent coinfection with other upper respiratory pathogens


CLINICAL PRESENTATION



DISEASE FORMS/SUBTYPES



• Pneumotropic isolates affect primarily the upper, and uncommonly the lower, respiratory tract.

• Rheumatic isolates cause joint pain and lameness in naturally infected kittens.
○ Joint disease also reported after administration of modified-live calicivirus vaccine

• Virulent systemic form may cause more severe clinical signs in adults.
○ Vaccinated cats can be affected.


HISTORY, CHIEF COMPLAINT



• Malaise: lethargy, listlessness

• Inappetence/anorexia
< div class='tao-gold-member'>

Related posts:

  1. D
  2. Y
  3. G
  4. N

Stay updated, free articles. Join our Telegram channel
Tags:
Jul 24, 2016 | Posted by in SMALL ANIMAL | Comments Off on C

Full access? Get Clinical Tree
Get Clinical Tree app for offline access