Liver disease often associated with superficial necrolytic dermatitis


Signalment: Canine, Sheltie, 11-year-old, female spayed, 32 lbs.


Canine, Sheltie, 11-year-old, female spayed, 32 lbs.

Photo's 1 - 4

Clinical history:

The dog presents today for a worsening skin disease that appears to be a necrolytic process occurring in the upper layers of the skin. The dog has had a history of several episodes of skin infections that have responded to antibiotics and medicated shampoo. Last month, the dog re-presented with a severe rash of the ventral abdomen and was treated with trimethoprim-sulfa drug combination for 14 days and a requested refill was done for an additional 10 days. No response in skin lesions has occurred. Last week, the skin disease was the worst seen and the affected areas were suspicious for an immune-mediated skin disease.

Physical examination:

The findings include rectal temperature 102.4° F, heart rate 115/min, respiratory rate 20/min, pink mucous membranes, normal capillary refill time, and normal heart and lung sounds. Abnormal physical findings are mild dental disease and multiple skin lesions (see the various skins lesions in the current images provided).

Laboratory results:

A complete blood count, serum chemistry profile and urinalysis were performed and are outlined in Table 1. Additional results from an ACTH stimulation test include are in Table 2:

Table 1: Results of laboratory tests

Radiographic review:

Survey thoracic and abdominal radiographs were done. The thoracic radiographs are normal. The abdominal radiographs show an enlarged liver and/or spleen.

Ultrasound examination:

Thorough abdominal ultrasonography was performed. The dog was positioned in dorsal recumbency for the ultrasonography. The ultrasound images provided are from this dog's liver.

Table 2:

My comments:

The liver shows an increase in mixed echogenicity with multiple hypoechoic lesions scattered throughout the liver parenchyma. Note the characteristic "Swiss cheese" pattern in the liver parenchyma. The gallbladder is mildly distended, and its walls are not thickened or hyperechoic.

The gallbladder does contain some sludge material. The spleen has uniform echogenicity - no masses noted. The left and right kidneys are similar in size, shape and echotexture. No masses or calculi were noted in either kidney. The urinary bladder is distended with urine and contains some urine sediment material - no masses or calculi noted. The stomach wall is normal.

Photo's 5 & 6

Case management:

In this case, hepatocutaneous syndrome is the clinical diagnosis. The following concise summary is provided by Dr. Rod A. W. Rosychuk, diplomate of ACVIM (internal medicine), Colorado State University, Fort Collins, Colo., and was presented at the 18th Annual ACVIM Veterinary Medical Forum in Seattle in 2000.

Hepatocutaneous syndrome

Hepatocutaneous syndrome, also known as superficial necrolytic dermatitis or metabolic dermatosis is an uncommon dermatosis seen in dogs and has been described rarely in the cat.

Superficial necrolytic dermatitis in dogs has been associated with hepatopathies in most cases. The most common hepatopathy is an idiopathic hepatocellular collapse. Other findings may include cirrhosis, hepatopathy secondary of ingestion of mycotoxins, and hepatopathy possibly associated with primidone or phenobarbital administration.

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Non-hepatic associations have included glucagon-producing pancreatic adenocarcinoma, hyperglucagonemia and glucagon-secreting liver metastases, and gastric carcinoma. Affected dogs may become diabetic, although the cause of the diabetes mellitus is not known. Idiopathic pancreatic atrophy has been noted.

Clinical signs and laboratory findings

Superficial necrolytic dermatitis is generally seen in middle-aged to older dogs - average being 10 years old. Males are more commonly affected. The history of skin lesions may span weeks to several months and may wax and wane. Skin lesions are usually noted to first affect the feet - interdigital erythema, crusting, erosions, hyperkeratosis, fissuring of footpads. Toenail loss has been noted.

Skin lesions may become pruritic and painful. Symmetric erythema, alopecia, crusts, and erosions/ulcers may be noted around the mouth, muzzle, eyes, hocks and elbows, pressure points, vulva and scrotum. Bulla-like lesions may be noted. Bullae appear to represent necrotic epidermal tissue and are not usually filled with appreciable amounts of purulent material. The skin lesions are prone to secondary staphylococcal and Malassezia infections, secondary candidiasis and dermatophytosis. The importance of the underlying disease in the predisposition to these infections is the observation that therapy for the underlying disease may result in the spontaneous resolution of the secondary infections.

Skin lesions have a characteristic histopathologic appearance of marked diffuse parakeratosis; marked ballooning degeneration of the upper layers of the stratum spinosum (intracellular and extracellular edema of the upper layers of the epidermis); edematous spaces are filled with neutrophils, necrotic epithelial cells and eosinophilic debris; marked epidermal hyperplasia; and mild neutrophilic perivascular inflammation in the superficial dermis. These changes have been termed the red (parakeratosis), white (edema) and blue (hyperplasia) sign suggestive of superficial necrolytic dermatitis.

Most dogs with superficial necrolytic dermatitis have pre-existing liver disease. Clinical signs related to the liver disease vary from no signs to weight loss, depression, lethargy, PU/PD, jaundice and anorexia. There is often a mild to moderate nonregenerative anemia to a mildly regenerative anemia. The serum chemistry profile will usually show increases in serum liver enzymes in 95 percent of cases characterized by increases in both serum alkaline phosphatase (ALP) and serum alanine aminotransferase (ALT).

Hypoproteinemia and fasting hyperglycemia are common but only a small percentage is overtly diabetic at time of initial diagnosis. If euglycemic at presentation, a fasting hyperglycemia will generally develop in the future.

If diabetes mellitus is encountered, it is usually late in the course of superficial necrolytic dermatitis. It is uncommon to see dogs proceed to the development of diabetic ketoacidosis. Increased serum glucagon concentrations have been noted in about 30-40 percent of affected dogs, and hypoaminoacidemia has been present in 85-90 percent of cases. Serum bile acids are abnormal in most cases.

Ultrasonography of the liver generally show a characteristic "Swiss cheese" pattern that some feel is pathognomonic for superficial necrolytic dermatitis. In dogs with idiopathic hepatocellular collapse as the cause for their liver disease, the liver is usually grossly nodular.

Histopathologically, there is moderate to severe hepatocellular collapse and vacuolar degeneration accompanied by nodular regeneration. This severe hepatic vacuolar alteration suggests a metabolic or hormonal disease, but the initiating cause has not been established. In some dogs, the liver is classically cirrhotic.

Clinical signs

Clinical signs associated with glucagonomas include depression, anorexia, diarrhea, vomiting, weight loss, and a normocytic, normochromic anemia. Increased serum liver enzymes may be seen in 40-50 percent of cases; hyperglycemia is very common with overt diabetes mellitus in about 30 percent of cases. Hyperglucagonemia, hypoalbuminemia and hypoaminoacidemia are very common. Abnormal serum bile acids are usually not found. A pancreatic mass is usually noted in a small percentage of cases based on abdominal ultrasonography.


The diagnosis of the skin disease is based on histopathologic examination. Skin lesions should not be surgically prepared for biopsy, and biopsies should come from the margins and lesional areas. Skin lesions should routinely have cytologic preparations of skin scrapings/impression smears/tape preparations to document secondary Malassezia, staphylococcal and Candida infections. Samples for dermatophyte cultures are taken.

Support for a diagnosis of an underlying hepatopathy is based on the results of the CBC, serum chemistry profile, urinalysis, serum bile acids, radiography, ultrasonography and liver biopsy results. Support for a diagnosis of glucagonoma is based on CBC, serum chemistry profile, urinalysis, serum bile acids, radiography, ultrasonography, CAT scan, arteriography, measurement of plasma glucagon (usually five to 10 times above the normal range) and exploratory surgery. In either liver- or glucagonoma-related cases, consideration should be given to measuring amino acids, zinc and fatty acids.


The treatment for superficial necrolytic dermatitis should include the following for consideration:

  • Diet high in good quality protein (e.g. supplement with Hill's a/d or a similar diet).

  • Enteral or parenteral feeding procedures may be needed.

  • Manage diabetes mellitus if present and the response to the insulin may be erratic.

Symptomatic treatment for secondary infections (systemic antibiotics and germicidal shampoo - if secondary bacterial pyoderma use benzoyl peroxide or if benzoyl peroxide is irritating, chlorhexidine shampoo; if secondary Malassezia, consider miconazole or ketoconazole shampoo). Exudative lesions may be treated with a germicidal/astringent soak (one part chlorhexidine to three parts Domeboro solution).

Amino acid supplementation

Egg yolk supplementation (three to six yolks daily) has been noted to be of some benefit, perhaps because of the amino acid profile provided. Others have used protein supplements favored by human body builders.

Intravenous amino acid therapy has been noted to benefit dogs with hepatopathy-related superficial necrolytic dermatitis. Aminosyn 10% Crystalline Amino Acid Solution from Abbott Laboratories is used for this purpose. Each 100 ml contains a total of 10 grams of amino acids. Use 500 ml per dog administered slowly over about eight to 12 hours in a large central vein, such as the external jugular vein.

Consideration should be given to measuring serum bile acids prior to this amino acid infusion in that it is possible to contribute to hepatic encephalopathy with this therapy. If significant improvement is noted, no further amino acid infusions are given.

Prolonged remissions have been noted after only a single infusion. If minimal to no response is noted, the infusions are repeated every seven to 10 days for four treatments. If an individual dog does not respond by this time, they will generally not respond. The amino acid infusion is repeated with each exacerbation of the skin lesions. Dogs may go several months between amino acid infusions, but some dogs will require monthly infusions to maintain remission. As the disease progresses, the need for amino acid infusions will likely increase.

Essential fatty acid supplementation is used primarily with omega 3 fatty acids at twice the bottle dosage of a high potency omega 3 fatty acid supplement.

Zinc supplementation of 2 mg/kg daily of zinc methionine is instituted in all individuals.

Niacinamide therapy may also be used at 250-500 mg/dog BID to TID.

For focal inflammatory lesions, such as pododermatitis, that have been controlled, consider the use of topical glucocorticoids, such as initially generic triamcinolone acetonide BID. Gradually, reduce the frequency of use and, if possible, switch to hydrocortisone for long-term maintenance therapy.

Systemic steroids (prednisone starting at 1 mg/kg daily) may be beneficial for some dogs. Effects are usually transient and will eventually become refractory to these therapeutic dosages.

Ketoconazole as been used with some benefit at 5-10 mg/kg BID because of its effects on secondary Malassezia infections or perhaps for its anti-inflammatory and antipruritic effects.

The treatment for glucagonoma-related superficial necrolytic dermatitis includes supportive care, treating the diabetes mellitus if present, surgical debulking/removal of the primary pancreatic tumor, octreotide (a long-acting analog of somatostatin that temporarily inhibits glucagon secretion), intravenous amino acid therapy as for the liver-related superficial necrolytic dermatitis, and zinc and fatty acid supplementation as for the liver-related superficial necrolytic dermatitis.


The prognosis for dogs with idiopathic hepatocellular collapse is generally poor. Even with the amino acid therapies and other supportive care, longest survivals have been not more than 2.5 years. The prognosis for glucagonoma-related superficial necrolytic dermatitis is generally grave. Most of these dogs already have metastatic disease at the time of diagnosis or will develop metastatic disease.

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