KEY BISCAYNE, FLA. — The 71-year-old woman's laboratory findings included a hemoglobin of 9.8 g/dL, an erythrocyte sedimentation rate of 94 mm/hr, and a fasting blood sugar level of 163 mg/dL. Her total serum protein was 4.2 g/dL (normal range, 6-8 g/dL), and her plasma glucagon was 405 pg/mL (normal range, 50-200 pg/mL).
Histology showed significant changes in upper skin strata, spongiosis, minor blister formations, and significant parakeratosis.
Abdominal CT scan and abdominal sonogram were negative. “I almost had to beg one of my surgeons to do a laparotomy,” Paul R. Vandersteen, M.D., said at the annual meeting of the Noah Worcester Dermatological Society. Endoscopy showed a large encapsulated tumor, 5 by 4 by 3 cm, at the head of the pancreas. There were no metastases.
Her diagnosis was glucagonoma syndrome, a rare α-cell tumor of the pancreas; there are only about 400 reported cases. The syndrome typically arises in a person's fifth decade. “What is striking in the [two] patients I've seen … is the significant pain, similar to a burn,” said Dr. Vandersteen, a dermatologist at MeritCare Medical Group in Fargo, N.D.
Necrolytic migratory erythema (NME) is the hallmark sign and the overall incidence of NME is 57% and up to 77% at initial presentation. It typically appears periorally or perinasally, as well as on the lower abdomen, perineum, genitals, and lower extremities. Generally, the erythematous patch follows a 7- to 14-day cycle during which it blisters centrally, erodes and crusts over, and heals with hyperpigmentation.
Glucagonoma is also known as the 4D syndrome, for dermatitis, diabetes, depression, and deep venous thrombosis. In addition to NME and diabetes mellitus, the most common presenting symptoms are weight loss, cheilosis, stomatitis, diarrhea, weakness, and mental changes. Laboratory signs include hypoaminoacidemia and hypoproteinemia, said Dr. Vandersteen, who is also a clinical professor of medicine at the University of North Dakota, Grand Forks.
The differential diagnosis includes acrodermatitis enteropathica, essential fatty acid deficiency, annular chronic lupus erythematosus, adverse drug reactions, contact dermatitis, and various vitamin deficiencies.
Imaging is helpful for diagnosis, particularly endoscopic ultrasonography and abdominal CT scans, “but remember, ours was negative,” Dr. Vandersteen said. Other imaging modalities are less useful, such as angiography, transabdominal ultrasound, or somatostatin receptor scintigraphy.
Treatment was a partial pancreatectomy. Postoperatively, the patient developed another deep venous thrombosis. Her glucagon level decreased significantly to 126 pg/mL at 4 days. Her NME gradually resolved over the following month.
Seven years after initial presentation the patient had pancreatic surgery. Mean survival is 3-7 years, but some live up to 20 years. Another 7 years later, she was hospitalized and a large mass was detected. Dr. Vandersteen said, “They decided to do nothing; she went home and succumbed 2 days later.”