Introduction

• Very rare condition in dogs.
• Cause: in humans is a paraneoplastic dermatosis usually associated with glucagonomas, in dogs associated with several hepatopathies, diabetes, Cushing's syndrome.
• Signs: dermatological signs at typical sites (feet, muzzle, axilla, inguinal, anogenital area); signs of underlying hepatic pathology, diabetes mellitus.
• Diagnosis: signs, laboratory tests of hepatic function, skin histopathology.
• Treatment: management of underlying disease, symptomatic care.
• Prognosis: poor.

Pathogenesis

Etiology

• Underlying hepatopathy:
  • Cirrhosis Liver: cirrhosis.
  • Chronic hepatitis Liver: chronic disease - overview Liver: chronic hepatitis.
• Diabetes mellitus Diabetes mellitus.
• Pancreatic neoplasia Pancreas: neoplasia.
• Chronic pancreatitis Pancreatitis: acute.
• Glucagonoma Pancreas: neoplasia (rare in dogs).

Pathophysiology

• In humans commonly associated with glucagonoma and removal of tumor results in resolution of lesion.
• Rare reports of glucagonoma association in dogs.
• Metabolic disorder of epidermis.

• Proposed pathogenesis: a metabolic defect (elevated glucagon, amino acid deficiency and/or zinc deficiency) responsible for epidermal necrosis.
• Increased glucagon levels→ increased gluconeogenesis and then amino acid utilization → cell starvation and necrosis. The sustained gluconeogenesis associated with hyperglucagonemia results in excessive protein and amino acid utilization (especially niacin and tryptophan which is required for glucagon synthesis). Hypoaminoacidemia (found in 97% of human cases of NME) is thought to result in epidermal depletion and consequent cutaneous necrosis.
• Mechanism of development of condition is poorly understood. Several suggestions:
  • In clinical cases there is increased [arachidonic acid] in epidermis which may be the result of increased [glucagon].
  • Local inflammation may → release of inflammatory mediators?
  • Skin lesions may arise as a result of decreased [amino acids] and [zinc] in plasma and skin: malabsorption/maldigestion as a result of abnormal hepatic/pancreatic function.
  • Sequestering of tryptophan into glucagonomas.

Timecourse

• Weeks to months.

Diagnosis

Treatment

Outcomes