May 2006

Fig.5

Fig.6

Diagnosis: Necrolytic Migratory Erythema associated with Glucagonoma

Based on his history of new-onset diabetes mellitus, the patient underwent an abdominal CT scan which revealed a pancreatic mass. He underwent a partial pancreatectomy with a Whipple procedure to resect a gluagonoma. His initial rash improved markedly following resection of the tumor; however, three years later the rash returned, and on further work-up the patient was noted to have metastases to the liver. He then underwent a partial liver resection and chemoembolization, which again improved the rash. To date, he continues to have flares of his rash coinciding with recurrence of his tumor burden; each relapse is treated with repeat chemoembolization, though he unfortunately continues to have steady progression of his disease.

Histopathology: The patient's skin biopsies revealed the typical changes of necrolytic migratory erythema (Figs. 5,6) including acanthosis with upper epidermal necrolysis, prominent intracellular edema, and loss of the granular cell layer. Neutrophilic chemotaxis to the necrotic epidermis can result in subcorneal pustules. The epidermis often shows a broad parakeratotic scale.

Necrolytic migratory erythema is most often associated with a glucagon-secreting alpha cell tumor of the pancreas. The cutaneous manifestations often precede all other symptoms of pancreatic carcinoma by several years. Unfortunately, at least 50% of patients already have metastatic disease at the time of diagnosis(2). Systemic symptoms include hyperglycemia, anemia, weight loss, diarrhea, glossitis, angular cheilitis, and thromboenbolism.

Necrolytic migratory erythema shows erythema, erosions, and vesicles which coalesce into large crusted plaques. The lesions rapidly heal and develop in new areas; there is marked daily fluctuation of the eruption. Skin lesions are classically seen on the face in the perioral and perinasal distribution, perineum, genitals, shins, ankles, and feet (3). These lesions can be very pruritic and painful. The distribution can be very similar to that of acrodermatitis enteropathica (4). Other conditions with a similarly appearing cutaneous eruptions include subcorneal pustular dermatosis, benign familial chronic pemphigus (Hailey-Hailey disease), kwashiorkor, and pellagra.

Laboratory findings include elevated glucagons levels, low serum zinc levels, and hypoaminoacidemia. Localization of the pancreatic primary tumor and metastatic disease is performed primarily with CT scanning, MRI, and ultrasonography. Somatostatin analogues can be used in conjunction with imaging to help identify both the primary lesion and any metastatic disease.

Necrolytic migratory erythema is poorly responsive to topical therapy. Amino acid, zinc, and essential fatty acid supplementation improves the eruption without lowering glucagons levels. Surgical resection of the tumor is standard of care and leads to resolution of the eruption (5). There has been some success with administering potent inhibitors of glucagon release and glucagon action, such as somatostatin. When the tumor is disseminated, surgical management is used to palliate cutaneous manifestations. Hepatic artery embolization may induce selective necrosis of hepatic metastases and also improve the skin disease. Finally, liver transplantation with pancreatectomy may be considered if the metastatic spread is confined only to the liver.

References:
1. Weedon D. Skin Pathology (2nd ed). Churchill-Livingstone,2002.
2. Pujol RM. Necrolytic migratory erythema: clinicopathologic study of 13 cases.
Int J Dermatol. 2004 Jan;43(1):12-8.
3. Andrew's Diseases of the Skin (10th Edition). Elsevier Inc, 2006.
4. Topham EJ. Exfoliative erythema of malnutrition with zinc and essential amino acid deficiency. Clin Exp Dermatol. 2005 May;30(3):235-7.
5. Zhang M. Clinical experience in diagnosis and treatment of glucagonoma syndrome.
Hepatobiliary Pancreat Dis Int. 2004 Aug;3(3):473-5. Review.

This case was prepared for presentation by Dr. Erica Rogers.

Presented by Dr. Beatriz Tapia