(superficial necrolytic dermatitis, necrolytic migratory erythema, metabolic epidermal necrosis, diabetic dermatopathy)
- Hepatocutaneous syndrome is an uncommon disease in dogs and very rare in cats.
- The majority of cases are associated with chronic liver disease with a much smaller number being caused by a glucagon secreting pancreatic neoplasm. In a survey of 75 cases in the veterinary literature only six were caused by a pancreatic neoplasm (Miller, Grif n and Campbell, 2013).
- The pathogenesis is incompletely understood. In the case of pancreatic neoplasia, increased gluconeogenesis may be caused by hyperglucagonaemia. With liver disease there may be increased catabolism of amino acids.
- With both diseases the end result is low plasma amino acid concentrations and depletion of epidermal protein, which is thought to be the cause of skin lesions.
Clinical features
- Signs of ill health may be apparent at initial presentation or a few months after the skin lesions.
- Polydipsia.
- Polyuria.
- Concurrent diabetes mellitus may be present with the above signs.
- Skin lesions are variable and include crusting, erosions and ulcers commonly occurring in the periocular and perinasal areas (Figures 1 and 2) and mucocutaneous junctions. There is usually marked hyperkeratosis of the footpads with ulceration and fissures (Figure 3). These lesions are painful and are often the trigger for requesting veterinary advice.
Differential diagnosis
(from Hnilica, 2011)
- Cutaneous epitheliotropic lymphoma
- Pemphigus foliaceus
- Pemphigus vulgaris
- Systemic lupus erythematosus
- Drug eruption
- Pedal pyoderma with an underlying cause (dermatophytosis, demodicosis)
- Zinc-responsive dermatosis
Diagnosis
- Blood samples may reveal a non-regenerative anaemia and in the case of an underlying hepatopathy there will usually be an increase in serum alkaline phosphatase, alanine aminotransferase, total bilirubin and bile acids. Hyperglycaemia is also possible.
- The most useful diagnostic tests in practice are abdominal ultrasonography and skin biopsy. With liver disease there are hypoechoic regions surrounded by hyperechoic areas giving rise to a honeycomb pattern which is very suggestive. Pancreatic neoplasia may also be detected either in situ or as liver metastases.
- Skin biopsy, particularly if performed early, is diagnostic in many cases. There is parakeratosis, oedema in the stratum spinosum caused by vacuolated keratinocytes and a deeply basophilic basal layer. This gives rise to a “red, white and blue pattern” sometimes called the “French ag”.
- Liver biopsy will identify the type of hepatopathy.
- Glucagon concentrations will be elevated in pancreatic neoplasia cases but may or may not be elevated with hepatopathy.
- Plasma amino acid concentrations are markedly decreased.
Treatment
- Rarely, in the case of a benign pancreatic tumour such as glucagonoma, surgical resection of the tumour is curative.
- With chronic hepatic disease an attempt should be made to identify an underlying cause, such as mycotoxins or anticonvulsant drug hepatotoxicity. Most cases do not have an identifiable underlying cause and in these symptomatic hepatic supportive treatment may prolong survival with drugs such as S-adenosylmethionine (sAME) or Ursodiol.
- Parenteral amino acid supplementation is the treatment of choice for improving skin lesions in animals with an underlying hepatopathy (Hnilica, 2011). 10% crystalline amino acid solution, or 3% amino electrolyte solution, both at a dose of 25mL/kg intravenously are administered over eight hours. This treatment is repeated every seven to 10 days with improvement in skin lesions to be expected within one to three weeks.
- A less effective alternative (Hnilica, 2011) is oral supplementation with three to six raw egg yolks per day together with zinc and essential fatty acid supplementation.
- As the hepatopathy is usually irreversible, the prognosis is very poor with survival time after the onset of skin lesions a few months only in the majority of cases. There is, however, a recent report of prolonged survival in a dog (Bach and Glasser, 2013). This case was managed for 24 months with a combination of oral fatty acid and protein supplements, intravenous amino acid infusion and intravenous lipid infusion. The authors suggest that the addition of lipid to the treatment regime was highly beneficial and to the best of their knowledge had been reported previously in the veterinary literature.
References and suggested reading
- Bach, J. A. and Glasser, S. A. (2013) A case of necrolytic migratory erythema managed for 24 months with intravenous amino acid and lipid infusions. Can Vet J. 54 (9): 873-875.
- Hnilica, K. A. (2011) Hepatocutaneous syndrome. In: Small Animal Dermatology. A Color Atlas and Therapeutic Guide, 3rd edition, 387-385. Elsevier.
- Miller, W. H., Grif n, C. E. and Campbell, K. L. (2013) Necrolytic Migratory Erythema. In: Muller and Kirk’s Small Animal Dermatology, 7th edition, 540-542. Elsevier.
