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Hepatocutaneous syndrome: When liver dysfunction affects skin

May 1, 2001
Alice M. Jeromin, RPh, DVM, DACVD

I love word derivations. For example, "hepato" means liver and "cutaneous" denotes skin. Quickly tying the two together, one is suspicious of a relationship between the two organs.

I love word derivations. For example, "hepato" means liver and "cutaneous" denotes skin. Quickly tying the two together, one is suspicious of a relationship between the two organs.

Photos 1 and 2: Extreme hyperkeratosis of footpads in two patients with hepatocutaneous syndrome.

The syndrome named hepatocutaneous syndrome also has other names including necrolytic migratory erythema (NME) and superficial necrolytic dermatitis (SND). This disease has been recognized in dogs (and reported in one cat) as well as humans with some differences and similarities in each species.

Hepatocutaneous syndrome is most often seen in aged dogs. The clinical presentation includes crusting of the perioral, periocular, perineal areas and/or footpads. Often the footpads are so thickened and crusty that it is difficult for the patient to ambulate. The feet may have a strong odor despite the owners trying to keep them clean via soaks and washing.

Photo 3: Crusting of the caudual thighs and perineal area in an affected patient.

Occasionally, the patient will be depressed or weak with a reduced appetite. Any breed may be affected but our practice has seen Miniature Poodles, Lhasa Apsos and Cocker Spaniels most commonly. Although some patients appear weakened from accompanying anemia, patients with underlying Cushing's disease and/or diabetes mellitus that present with hepatocutaneous syndrome, may be polyuric, polyphagic and polydipsic.

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Identifying the disease

Skin biopsies may offer the first indication of the presence of hepatocutaneous syndrome. The biopsy results indicate a "red, white and blue" sign characteristic of an overlying hemorrhagic crust topping edema under which is an accumulation of neutrophils. It is this characteristic biopsy finding that suggests we look further for underlying liver or pancreatic problems. Serum profiles may show elevated liver enzymes, hypercholesterolemia, hypertriglyceridemia or elevated serum glucose. Complete blood counts may show an elevated blood glucose and normocytic normochromic anemia due to chronic disease. Urinalysis may confirm diabetes via glucosuria, proteinuria and/or ketonuria depending on the stage of diabetes.

In essence, there is usually underlying liver or pancreatic pathology indicating a primary liver or pancreatic tumor (glucagonoma), diabetes mellitus or Cushing's disease. Radiographs or abdominal ultrasounds are useful to determine if a tumor is present.

Photo 4: Ventral view of perineum and thighs of same patient in photo 3. Note the crusting and occasional ulceration.

In humans, it is more common to have a pancreatic tumor (glucagonoma) but in our canine patients, liver pathology is more common. Ideally, if the underlying liver or pancreatic problem can be resolved, the skin pathology will be corrected. This is often more successful in patients with Cushing's disease or diabetes mellitus as once the disease is brought under control, the skin lesions may dissipate. However when neoplasia is involved, the skin lesions may persist and be quite painful.

A recent report from France of four patients with hepatocutaneous syndrome, found no liver or pancreatic abnormalities on necropsy in two of the patients. The presence of skin lesions therefore can also be a "reaction" to a metabolic change in the body.

For example, occasionally humans with Crohn's disease will develop lesions of hepatocutaneous syndrome yet there is no underlying liver or pancreatic pathology.

Skin lesions

There are theories of why skin lesions occur in some patients with hepatic or pancreatic dysfunction.

Most of these have been studied in humans and their findings extrapolated to our canine patients. The liver manufactures protein and fatty acids that are then transported to the skin via the blood stream. When liver pathology is present in some patients, the transfer of fatty acids and protein does not occur and the skin becomes deficient.

In humans, a deficiency in skin zinc levels may also be present. These factors may explain why aside from addressing the underlying liver or pancreatic problem, treatment includes protein replenishment, fatty acids and zinc supplementation. Protein replenishment involves using proteins in their most elemental form, amino acids. Amino acid tablets, egg yolks or intravenous hyperalimentation solutions (Aminosyn) are examples of elemental protein replenishment. Fatty acid supplementation includes omega 3, 6 fatty acids such as DermCaps or EFA Caps.

Since liver disease can result in nausea and anorexia in some patients and in some severe anemia is present, often just getting the patient to eat is a challenge. Foot soaks or topical emollients may be helpful in softening the crusted footpads and if secondary yeast is present, topical anti-yeast sprays or shampoos may be used. Steroids are controversial since they can cause further liver pathology yet may reduce the edema and swelling of the skin lesions.

The prognosis of a patient with hepatocutaneous syndrome is guarded, and if underlying neoplasia is present many times the best we can do is to keep him/her comfortable. Since clinically the patient presents with signs similar to pemphigus foliaceus or zinc responsive dermatosis, a skin biopsy is necessary to distinguish between the diseases.

Hepatocutaneous syndrome is usually seen in elderly patients with serum profile abnormalities whereas patients with pemphigus foliaceus and zinc responsive dermatosis often have normal serum profiles.

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