Glucagonoma syndrome refers to the constellation of signs and symptoms that develop in the setting of an underlying glucagonoma, a rare, slow-growing functional neuroendocrine tumor of the pancreatic alpha cells. Excessive glucagon production from tumor cells leads to these clinical manifestations, which include necrolytic migratory erythema (NME), diabetes mellitus, weight loss, anemia, diarrhea, venous thrombosis, and neuropsychiatric disturbances. 

NME is the presenting manifestation in over 90% of glucagonoma cases, and it often precedes tumor diagnosis. It classically presents with migrating, annular, erythematous papules, patches, and plaques with superficial necrosis leading to erosions and bullae. The eruption is most commonly located in intertriginous areas. Pruritus and a burning sensation have been reported. Lesions may improve spontaneously and reappear months later, and clinical improvement also occurs after surgical excision or surgical debulking of the pancreatic lesion.

Importantly, NME can also occur without glucagonoma. Cases have been associated with inflammatory bowel disease (Crohn disease, ulcerative colitis), chronic liver disease, pancreatitis, nonpancreatic malignancies, and disorders of malabsorption.

The pathophysiology of NME is not fully understood but is likely multifactorial, involving excess glucagon and/or deficiency of amino acids, zinc, and free fatty acids.