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Migratory necrolytic erythema and glucagonoma
Migratory necrolytic erythema and glucagonoma Miguel Echenique-Elizondo, MD, FACS, Jose Luis Elorza, MD, and Jorge Soto de Delas, MD, San Sebastián, Spain
From the Basque Country University School of Medicine, San Sebastián, Spain
A 72-YEAR-OLD woman presented with an 11-year history of a waxing and waning scaling rash that principally involved her face (Fig 1) and extremities (Fig 2), along with glossitis. The diagnosis of migratory necrolytic erythema was made on biopsy of the skin. Routine blood tests were normal except for an elevated fasting blood sugar of 145 mg/dL. Basal plasma glucagon was 1100 pg/mL (normal, 55-177), and serum zinc was 97 µg/dL (normal, 60-150). An abdominal computed tomography scan showed a 4-cm mass in the body of the pancreas but no evidence of metastases. During somatostatin infusion, plasma glucagon levels dropped to 673 pg/mL. Distal pancreatectomy and splenectomy were performed. There were no metastases found. Postoperative plasma glucagon levels were 222 pg/mL. The skin rash cleared immediately, and the patient is free of recurrence at 36 months postoperatively. DISCUSSION Migratory necrolytic erythema is an uncommon condition sometimes associated with high plasma levels of circulating glucagon. It is a component of the glucagonoma syndrome, a paraneoplastic phenomenon characterized by a pancreatic islet alphacell tumor, diabetes mellitus, weight loss, anemia, stomatitis, thromboembolism, and gastrointestinal and neuropsychiatric disturbances. Glucagon itself is responsible for most of the observed signs and symptoms, and its induction of hypoaminoacidemia is thought to lead to migratory necrolytic erythema. Liver disease and fatty acid and zinc deficiency states may also contribute to the pathogenesis of the eruption in some cases.1,2
Fig 1. Migratory necrolytic erythema involving the face.
Fig 2. Migratory necrolytic erythema on the arm.
Accepted for publication March 6, 2002. Reprint requests: M. Echenique-Elizondo, MD, FACS, Associated Professor of Surgery, Basque Country University, Unidad Docente de Medicina de San Sebastián, Paseo Dr. Beguiristain, 105, 20014 San Sebastián, Spain. Surgery 2003;133:449-50. © 2003 by Mosby, Inc. All rights reserved 0039-6060/2003/$30.00 + 0 doi:10.1067/msy.2003.51
Fig 3. Surgical specimen, distal pancreas, and spleen. SURGERY 449
450 Echenique-Elizondo, Elorza, and Soto de Delas
Most patients are diagnosed too late in the clinical course for cure, but successful palliation of symptomatology can usually be achieved with surgical debulking and pharmacologic suppression. Because glucagonomas, like other neuroendocrine tumors, express somatostatin receptors in more than 80% of cases, suppression of glucagon secretion by long-acting somatostatin analogues such as octreotide offers a therapeutic avenue even for metastatic disease.3 Control of liver metastases by metastasectomy,3 cryoablation,4 radiofrequency ablation, or chemoembolization has been reported. Intravenous amino acid supplementation may relieve or temporarily cure the unsightly and uncomfortable rash. There have been limited reports in the literature supporting the use of indium In-111 DTPA N-terminal D-phenylalanine (D-PHE1) octreotide for glucagonoma imaging, but because of the rarity of these tumors, the sensitivity and the specificity of somatostatin analog (octreotide) imaging has not
Surgery April 2003 been established.5 Somatostatin-receptor imaging may be helpful as an adjuvant to conventional computed tomography imaging and positron emission tomography for tumor staging and therapeutic decisions. REFERENCES 1. Bernstein M, Jahoor F, Townsend CM Jr, Klein S. Amino acid, glucose, and lipid kinetics after palliative resection in a patient with glucagonoma syndrome. Metabolism 2001;50:720-2. 2. Sinclair SA, Reynolds NJ. Necrolytic migratory erythema and zinc deficiency. Br J Dermatol 1997;136:783-5. 3. Lipp RW, Schnedl WJ, Stauber R, Ranner G, Leb G, Krejs GJ. Scintigraphic long-term follow-up of a patient with metastatic glucagonoma. Am J Gastroenterol 2000;95:1818-20. 4. Hellman P, Andersson M, Rastad J, Juhlin C, Karacagil S, Eriksson B, et al. Surgical strategy for large or malignant endocrine pancreatic tumors. World J Surg 2000;24:1353-60. 5. El Rassi Z, Partensky C, Valette PJ, Berger F, Chayvialle JA. Necrolytic migratory erythema, first symptom of a malignant glucagonoma: treatment by long-acting somatostatin and surgical resection. Report of three cases. Eur J Surg Oncol 1998;24:562-7.
From the Basque Country University School of Medicine, San Sebastián, Spain
A 72-YEAR-OLD woman presented with an 11-year history of a waxing and waning scaling rash that principally involved her face (Fig 1) and extremities (Fig 2), along with glossitis. The diagnosis of migratory necrolytic erythema was made on biopsy of the skin. Routine blood tests were normal except for an elevated fasting blood sugar of 145 mg/dL. Basal plasma glucagon was 1100 pg/mL (normal, 55-177), and serum zinc was 97 µg/dL (normal, 60-150). An abdominal computed tomography scan showed a 4-cm mass in the body of the pancreas but no evidence of metastases. During somatostatin infusion, plasma glucagon levels dropped to 673 pg/mL. Distal pancreatectomy and splenectomy were performed. There were no metastases found. Postoperative plasma glucagon levels were 222 pg/mL. The skin rash cleared immediately, and the patient is free of recurrence at 36 months postoperatively. DISCUSSION Migratory necrolytic erythema is an uncommon condition sometimes associated with high plasma levels of circulating glucagon. It is a component of the glucagonoma syndrome, a paraneoplastic phenomenon characterized by a pancreatic islet alphacell tumor, diabetes mellitus, weight loss, anemia, stomatitis, thromboembolism, and gastrointestinal and neuropsychiatric disturbances. Glucagon itself is responsible for most of the observed signs and symptoms, and its induction of hypoaminoacidemia is thought to lead to migratory necrolytic erythema. Liver disease and fatty acid and zinc deficiency states may also contribute to the pathogenesis of the eruption in some cases.1,2
Fig 1. Migratory necrolytic erythema involving the face.
Fig 2. Migratory necrolytic erythema on the arm.
Accepted for publication March 6, 2002. Reprint requests: M. Echenique-Elizondo, MD, FACS, Associated Professor of Surgery, Basque Country University, Unidad Docente de Medicina de San Sebastián, Paseo Dr. Beguiristain, 105, 20014 San Sebastián, Spain. Surgery 2003;133:449-50. © 2003 by Mosby, Inc. All rights reserved 0039-6060/2003/$30.00 + 0 doi:10.1067/msy.2003.51
Fig 3. Surgical specimen, distal pancreas, and spleen. SURGERY 449
450 Echenique-Elizondo, Elorza, and Soto de Delas
Most patients are diagnosed too late in the clinical course for cure, but successful palliation of symptomatology can usually be achieved with surgical debulking and pharmacologic suppression. Because glucagonomas, like other neuroendocrine tumors, express somatostatin receptors in more than 80% of cases, suppression of glucagon secretion by long-acting somatostatin analogues such as octreotide offers a therapeutic avenue even for metastatic disease.3 Control of liver metastases by metastasectomy,3 cryoablation,4 radiofrequency ablation, or chemoembolization has been reported. Intravenous amino acid supplementation may relieve or temporarily cure the unsightly and uncomfortable rash. There have been limited reports in the literature supporting the use of indium In-111 DTPA N-terminal D-phenylalanine (D-PHE1) octreotide for glucagonoma imaging, but because of the rarity of these tumors, the sensitivity and the specificity of somatostatin analog (octreotide) imaging has not
Surgery April 2003 been established.5 Somatostatin-receptor imaging may be helpful as an adjuvant to conventional computed tomography imaging and positron emission tomography for tumor staging and therapeutic decisions. REFERENCES 1. Bernstein M, Jahoor F, Townsend CM Jr, Klein S. Amino acid, glucose, and lipid kinetics after palliative resection in a patient with glucagonoma syndrome. Metabolism 2001;50:720-2. 2. Sinclair SA, Reynolds NJ. Necrolytic migratory erythema and zinc deficiency. Br J Dermatol 1997;136:783-5. 3. Lipp RW, Schnedl WJ, Stauber R, Ranner G, Leb G, Krejs GJ. Scintigraphic long-term follow-up of a patient with metastatic glucagonoma. Am J Gastroenterol 2000;95:1818-20. 4. Hellman P, Andersson M, Rastad J, Juhlin C, Karacagil S, Eriksson B, et al. Surgical strategy for large or malignant endocrine pancreatic tumors. World J Surg 2000;24:1353-60. 5. El Rassi Z, Partensky C, Valette PJ, Berger F, Chayvialle JA. Necrolytic migratory erythema, first symptom of a malignant glucagonoma: treatment by long-acting somatostatin and surgical resection. Report of three cases. Eur J Surg Oncol 1998;24:562-7.