Page 643 - Small Animal Internal Medicine, 6th Edition

CHAPTER 36 Hepatobiliary Diseases in the Dog 615

is poor because there is no effective therapy. Hepatic tumors affected dogs was 10 years, and the median duration of phe-
also respond poorly to chemotherapy, likely partly because nobarbital therapy was 6 years. No other underlying cause
VetBooks.ir of the development of rapid drug resistance by neoplastic could be found. Plasma amino acid concentrations were
markedly decreased in the only dog in which they were
hepatocytes. The response of secondary (metastatic) liver
tumors depends on the type and location of the primary
Whatever the underlying pathogenesis, dogs with super-
tumor; responses in dogs with hepatic lymphoma as part of measured.
the multicentric form are very good to excellent, whereas ficial necrolytic dermatitis are at high risk of becoming dia-
presumed primary hepatic lymphoma had a poor response betic, which is reported in 25% to 40% of cases. This is easy
to chemotherapy in one recent study, with dogs not achiev- to explain if blood glucagon concentrations are high, because
ing complete remission and dogs with a low serum albumin glucagon is a diabetogenic hormone but is difficult to explain
concentration having particularly poor responses (Dank on the basis of simple amino acid level changes.
et al., 2011). Hemangiosarcoma metastases respond well to
vincristine, doxorubicin, and cyclophosphamide (VAC) che- Clinical Findings
motherapy (see Chapter 81). Metastatic carcinomas or car- Idiopathic superficial necrolytic dermatitis is usually reported
cinoids of the liver rarely respond to chemotherapy. (See in older dogs of small breeds; in one study 75% of the affected
“Oncology” for additional information on metastatic dogs were male (Outerbridge et al., 2002). Most dogs present
tumors.) because of their skin disease rather than their primary liver
disease. Typically, there is erythema, crusting, and hyper-
keratosis affecting the footpads, nose, and periorbital, peri-
HEPATOCUTANEOUS SYNDROME AND anal, and genital areas, and often pressure points on the
SUPERFICIAL NECROLYTIC DERMATITIS limbs. The paw lesions can be extremely painful because of
associated fissures and may result in lameness and secondary
Etiology and Pathogenesis infection. Signs of liver disease may also be present, although
Hepatocutaneous syndrome (also known as superficial not usually, and diabetes mellitus often develops later in the
necrolytic dermatitis, metabolic epidermal necrosis, and necro- disease process, especially if the animal is given diabetogenic
lytic migratory erythema) is a skin condition reported in drugs such as glucocorticoids in an attempt to control the
association with certain liver diseases that usually carries a skin disease.
poor prognosis. The pathophysiology and underlying causes
in dogs remain unclear, and it is likely multifactorial. It Diagnosis
occurs in association with certain typical findings on hepatic Definitive diagnosis is based on skin biopsy findings that are
ultrasonography and histopathology, and often no underly- characteristic and unique. The only syndrome with a similar
ing cause is found. However, because it is likely that many appearance on skin histopathology is zinc-responsive der-
cases represent a hepatic reaction to an underlying endo- matosis. There is a marked parakeratotic hyperkeratosis with
crine tumor or disorder, superficial necrolytic dermatitis intercellular and intracellular edema and hyperplastic basal
represents an intermediate disorder between primary liver cells, producing a characteristic red, white, and blue appear-
disease and secondary hepatopathies. ance on hematoxylin and eosin (H&E) staining.
The underlying pathogenesis in the skin appears to be The associated hepatic findings are more nonspe-
caused by abnormally low circulating amino acid concentra- cific, except for the ultrasonographic findings. There are
tions and thus malnutrition of the skin, particularly in areas usually increases in liver enzyme activities, and there may
of poor blood supply, such as the extremities. Zinc deficiency be hypoalbuminemia in some cases. In dogs that are dia-
may also be involved because the histologic appearance of betic, there is hyperglycemia and glycosuria. The typical
the skin is similar to that in dogs with zinc-responsive der- ultrasonographic appearance is a so-called Swiss cheese
matosis; fatty acid deficiencies have also been implicated. In liver consisting of multiple hypoechoic regions with hyper-
humans the disorder is usually associated with a glucagon- echoic borders (Fig. 36.17). Hepatic histology in all cases
secreting tumor of the pancreas. However, glucagonomas are is remarkably similar, showing what has been described as
rarely reported in affected dogs, and circulating glucagon a distinctive form of macronodular cirrhosis. The liver is
concentrations are usually normal, although they may be divided into regenerative hyperplastic nodules with fibrous
occasionally high. Plasma amino acid concentrations have septa and bordered by characteristic ballooned vacu-
been reported to be very low in all affected dogs in which olated hepatocytes but with minimal or no inflammation
they have been measured, both in dogs with pancreatic or necrosis.
tumors and dogs without. It has been proposed that canine
superficial necrolytic dermatitis represents a metabolic hepa- Treatment and Prognosis
topathy with increased hepatic catabolism of amino acids, The prognosis is very poor unless the underlying cause can
which decreases their peripheral availability. be identified and treated; most dogs live for less than 6
Superficial necrolytic dermatitis secondary to chronic months. There have been reports of disease resolution if a
phenobarbital administration for epilepsy has been reported pancreatic tumor is identified and removed. Dogs with
in 11 dogs (March et al., 2004). The median age of the phenobarbital-associated hepatocutaneous syndrome may