METABOLIC EPIDERMAL NECROSIS (HEPATOCUTANEOUS SYNDROME)
This disease (MEN) refers to a group of skin lesions and histological changes associated with an internal disease process. In the dog, MEN is usually associated with a vacuolar hepatopathy of unknown origin and much less frequently with glucagon-secreting tumors. In some cases, however, a hepatopathy due to the long-term use of anticonvulsant medications or to mycotoxin ingestion has been implicated. In the few cases involving the cat, MEN has been associated etiologically with pancreatic carcinoma, hepatopathies and thymic amyloidosis. The disease is typically seen in middle-aged to old animals with a history of relatively acute onset of alopecic, erythematous, exudative, coalescing papules and/or plaques with crusting, ulceration and occasionally vesiculation.
The lesions are usually located in the muzzle, distal extremities, footpads (hyperkeratosis, exfoliation, fissures, erosions), pressure points, mucocutaneous junctions and genitalia. Other noticeable signs are lethargy, partial anorexia and gradual weight loss. Polyuria and polydipsia are also seen, especially when the disease is complicated by diabetes mellitus, secondary to glucagonomas. Cutaneous lesions may precede the clinical onset of the underlying disease. A superficial perivascular to interface, cell-rich, dermatitis with marked diffuse parakeratotic hyperkeratosis and striking inter-and intracellular edema limited to the upper half of the epidermis are usually demonstrated by skin biopsies. Varying degrees of hypoaminoacidemia, hyperglucagonemia and hyperinsulinemia have been reported with both liver and pancreatic-associated MEN. Lack of specificity renders the diagnostic value of these tests questionable. In abdominal ultrasound, a "Swiss cheese" liver echotexture representing a hyperechoic network surrounding hypoechoic areas of parenchyma is diagnostic of vascular hepatopathy. This approach is frequently unremarkable in glucagonoma patients although pancreatic tumors or hepatic metastases are occasionally detected. Ultrasound-guided liver biopsies may reveal cirrhosis, vacuolar hepatopathy with cirrhosis, parenchymal collapse and nodular hyperplasia or toxic hepatopathy.
Unfortunately, the progression of the underlying hepatopathies is relentless but surgical excision of glucagonomas generally results in remission of all clinical signs although pancreatitis, biliary obstruction or metastatic disease may occur postoperatively. In an attempt to correct the nutritional deficit of epidermis, high-quality proteins (egg yolks, Hill's Prescription diet a/d, raw bovine or porcine pancreas) along with dietary zinc and fatty acid supplementation, are advocated. Intravenous amino acid supplementation, preferably as a hypertonic 10% crystalline solution (25 ml/Kg BW over 6-8 hours for 1-3 days) results in quick and effective decrease of pain and healing time of skin lesions. The use of octreotide for palliative control of glucagonoma-induced MEN is limited because of the expense and drug-resistance. Glucocorticoids aid in the resolution of the skin lesions but may cause a diabetic crisis. The long-term prognosis, especially if vacuolar hepatopathy is the underlying disease, is poor as most of the affected animals finally die up to 6 months from the time of diagnosis.
