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Glucagonoma syndrome: Diagnosis and treatment
LETTERS CASE
NOTES
Glucagonoma syndrome: Diagnosis and treatment To the Editor: A 46-year-old man presented with erythema, blisters, and glossitis for 3 years. The rash first appeared on both lower extremities and, during 3 years, had spread to the trunk, perineum, face, and upper extremities. Several skin biopsies were taken and eczema or psoriasis was once considered. He experienced a 10-kg weight loss in the 6 months before admission. Physical examination revealed a diffuse, dark-red, peripherally scaled eruption with fragile blisters (Fig 1). The eruption was distributed prevalently over perioral regions, perineum, and lower extremities, and presented a map-like margin (Fig 2). His tongue showed a beefy red appearance. Laboratory analysis revealed markedly increased serum glucagon at 1014.72 pg/mL (49.16-113.96 pg/mL), a mild hyperglycemia (120 mg/dL), glycosuria, and abnormal glucose tolerance. Skin histopathologic changes showed papillary epidermal necrosis with clear border to the underlying viable epidermis. Abdominal, B-type, ultrasonic, computerized tomographic and 99Tcm-octreotide scanning revealed the existence of original and metastatic tumors in the liver and tail of the pancreas. The patient was given a diagnosis of glucagonoma syndrome and Lanreotide (Ipsen Biotechnology Co, Paris, France) was administered intramuscularly at a dose of 30 mg every 10 days. Blood was obtained for plasma glucagon measurements at different times after the first injection of Lanreotide (Ipsen Biotechnology Co) (Fig 3). A marked decrease in circulation glucagon was noted, and the glucagon level reached its nadir at 12 hours. Accordingly, symptomatic improvement was noted within 2 to 3 days of Lanreotide (Ipsen Biotechnology Co) administration. The rash on the face became dry on the second day, and complete resolution of the rash occurred after 7 days. He did not experience aggravation of diabetes mellitus. The patient showed a nonspecific rash at the beginning, but a typical presentation of necrolytic migratory erythema and other systemic manifestation developed. As described by Kheir et al,1 necrolytic migratory erythema has different histopathologic changes. The most characteristic change is the epithelial superficial necrosis. The second common characteristic is subcorneal pustules that occur at or near the necrosis area, with or without acantholysis. The differential J AM ACAD DERMATOL
Fig 1. Peripherally scaled eruption on lower legs, covered with superficial, thin, and dark-brown necrolytic crusts.
Fig 2. Annular edematous erythemas over perineum regions presented map-like margin.
diagnosis should include impetigo, subcorneal pustular dermatosis, and pemphigus foliaceus. The third and mostly unrecognized pattern is FEBRUARY 2003 297
298 Letters
J AM ACAD DERMATOL FEBRUARY 2003
Fig 3. After initial intramuscular injection of 30 mg Lanreotide (Ipsen Biotechnology Co), plasma glucagon decreased from value of 1100 to 580 pg/mL at 30 minutes and 300 pg/mL at 12 hours, but began to increase afterwards.
psoriasiform hyperplasia with angioplasia, which simulates psoriasis. The presence of psoriasiform hyperplasia, striking capillary dermal angioplasia, and confluent parakeratosis differentiate glucagonoma from psoriasis, acrodermatitis enteropathica, and pellagra. Eczema is easily misdiagnosed, but dyskeratotic dermatitis in a chronic skin eruption is a clue to the diagnosis of necrolytic migratory erythema.2 This patient had the condition for 3 years, during which he was given the misdiagnosis of eczema and psoriasis. Therefore, it is important to recognize the variation of the histopathologic changes and take several biopsy specimens from the inner edge of an actively advancing border. Somatostatin is a potent endogenous inhibitor of peptide release. Although it has been shown to significantly decrease glucagon concentrations, its use has been limited by its short plasma half-life of only 3 to 4 minutes.3 Lanreotide (Ipsen Biotechnology Co), a new analog, has been recently reported to be effective in the treatment of glucagonoma syndrome; its biologic activity lasts 10 to 14 days.4 It has been shown to reduce serum glucagon and ameliorate symptoms, but it does not appear to suppress tumor growth. The serum glucagon change showed administration of Lanreotide (Ipsen Biotechnology Co) decreased glucagon markedly by 24 hours after injection, and though glucagon returned to the level found before therapy, the clinical symptoms remitted for 7 to 10 days.
Jianying Zeng, MD Baoxi Wang, MD Donglai Ma, MD Fang Li, MD Department of Dermatology Peking Union Medical College Hospital Beijing 100730, China We thank Gerald S. Lazarus, MD, for his expertise and valuable comments regarding this letter.
REFERENCES 1. Kheir SM, Omura EF, Grizzle WE, Herrera GA, Lee I. Histologic variations in the skin lesions of the glucagonoma syndrome. Am J Surg Pathol 1986;10:445-53. 2. Hunt SJ, Narus VT, Abell E. Necrolytic migratory erythema: dyskeratotic dermatitis, a clue to early diagnosis. J Am Acad Dermatol 1991;24:473-7. 3. Altimari AF, Bhoopalam N, O’Dorsio T, Lange CL, Sandberg L, Prinz RA. Use of a somatostatin analog (SMS 201-995) in the glucagonoma syndrome. Surgery 1986;100:989-96. 4. Tomassetti P, Migliori M, Gullo L. Slow-release lanreotide treatment in endocrine gastrointestinal tumors. Am J Gastroenterol 1998;93:1468-71. doi:10.1067/mjd.2003.73
Arcanobacterium haemolyticum To the Editor: Arcanobacterium haemolyticum is a nondiphtheroid corynebacterium with lipid-hydrolyzing enzymes. It is becoming an increasingly known agent of pharyngitis (pharyngitis etiology 0.5% to 2.5% of the time),1 often infecting adoles-
NOTES
Glucagonoma syndrome: Diagnosis and treatment To the Editor: A 46-year-old man presented with erythema, blisters, and glossitis for 3 years. The rash first appeared on both lower extremities and, during 3 years, had spread to the trunk, perineum, face, and upper extremities. Several skin biopsies were taken and eczema or psoriasis was once considered. He experienced a 10-kg weight loss in the 6 months before admission. Physical examination revealed a diffuse, dark-red, peripherally scaled eruption with fragile blisters (Fig 1). The eruption was distributed prevalently over perioral regions, perineum, and lower extremities, and presented a map-like margin (Fig 2). His tongue showed a beefy red appearance. Laboratory analysis revealed markedly increased serum glucagon at 1014.72 pg/mL (49.16-113.96 pg/mL), a mild hyperglycemia (120 mg/dL), glycosuria, and abnormal glucose tolerance. Skin histopathologic changes showed papillary epidermal necrosis with clear border to the underlying viable epidermis. Abdominal, B-type, ultrasonic, computerized tomographic and 99Tcm-octreotide scanning revealed the existence of original and metastatic tumors in the liver and tail of the pancreas. The patient was given a diagnosis of glucagonoma syndrome and Lanreotide (Ipsen Biotechnology Co, Paris, France) was administered intramuscularly at a dose of 30 mg every 10 days. Blood was obtained for plasma glucagon measurements at different times after the first injection of Lanreotide (Ipsen Biotechnology Co) (Fig 3). A marked decrease in circulation glucagon was noted, and the glucagon level reached its nadir at 12 hours. Accordingly, symptomatic improvement was noted within 2 to 3 days of Lanreotide (Ipsen Biotechnology Co) administration. The rash on the face became dry on the second day, and complete resolution of the rash occurred after 7 days. He did not experience aggravation of diabetes mellitus. The patient showed a nonspecific rash at the beginning, but a typical presentation of necrolytic migratory erythema and other systemic manifestation developed. As described by Kheir et al,1 necrolytic migratory erythema has different histopathologic changes. The most characteristic change is the epithelial superficial necrosis. The second common characteristic is subcorneal pustules that occur at or near the necrosis area, with or without acantholysis. The differential J AM ACAD DERMATOL
Fig 1. Peripherally scaled eruption on lower legs, covered with superficial, thin, and dark-brown necrolytic crusts.
Fig 2. Annular edematous erythemas over perineum regions presented map-like margin.
diagnosis should include impetigo, subcorneal pustular dermatosis, and pemphigus foliaceus. The third and mostly unrecognized pattern is FEBRUARY 2003 297
298 Letters
J AM ACAD DERMATOL FEBRUARY 2003
Fig 3. After initial intramuscular injection of 30 mg Lanreotide (Ipsen Biotechnology Co), plasma glucagon decreased from value of 1100 to 580 pg/mL at 30 minutes and 300 pg/mL at 12 hours, but began to increase afterwards.
psoriasiform hyperplasia with angioplasia, which simulates psoriasis. The presence of psoriasiform hyperplasia, striking capillary dermal angioplasia, and confluent parakeratosis differentiate glucagonoma from psoriasis, acrodermatitis enteropathica, and pellagra. Eczema is easily misdiagnosed, but dyskeratotic dermatitis in a chronic skin eruption is a clue to the diagnosis of necrolytic migratory erythema.2 This patient had the condition for 3 years, during which he was given the misdiagnosis of eczema and psoriasis. Therefore, it is important to recognize the variation of the histopathologic changes and take several biopsy specimens from the inner edge of an actively advancing border. Somatostatin is a potent endogenous inhibitor of peptide release. Although it has been shown to significantly decrease glucagon concentrations, its use has been limited by its short plasma half-life of only 3 to 4 minutes.3 Lanreotide (Ipsen Biotechnology Co), a new analog, has been recently reported to be effective in the treatment of glucagonoma syndrome; its biologic activity lasts 10 to 14 days.4 It has been shown to reduce serum glucagon and ameliorate symptoms, but it does not appear to suppress tumor growth. The serum glucagon change showed administration of Lanreotide (Ipsen Biotechnology Co) decreased glucagon markedly by 24 hours after injection, and though glucagon returned to the level found before therapy, the clinical symptoms remitted for 7 to 10 days.
Jianying Zeng, MD Baoxi Wang, MD Donglai Ma, MD Fang Li, MD Department of Dermatology Peking Union Medical College Hospital Beijing 100730, China We thank Gerald S. Lazarus, MD, for his expertise and valuable comments regarding this letter.
REFERENCES 1. Kheir SM, Omura EF, Grizzle WE, Herrera GA, Lee I. Histologic variations in the skin lesions of the glucagonoma syndrome. Am J Surg Pathol 1986;10:445-53. 2. Hunt SJ, Narus VT, Abell E. Necrolytic migratory erythema: dyskeratotic dermatitis, a clue to early diagnosis. J Am Acad Dermatol 1991;24:473-7. 3. Altimari AF, Bhoopalam N, O’Dorsio T, Lange CL, Sandberg L, Prinz RA. Use of a somatostatin analog (SMS 201-995) in the glucagonoma syndrome. Surgery 1986;100:989-96. 4. Tomassetti P, Migliori M, Gullo L. Slow-release lanreotide treatment in endocrine gastrointestinal tumors. Am J Gastroenterol 1998;93:1468-71. doi:10.1067/mjd.2003.73
Arcanobacterium haemolyticum To the Editor: Arcanobacterium haemolyticum is a nondiphtheroid corynebacterium with lipid-hydrolyzing enzymes. It is becoming an increasingly known agent of pharyngitis (pharyngitis etiology 0.5% to 2.5% of the time),1 often infecting adoles-