BACKGROUND
A previously healthy 70-year-old woman presented to her primary care physician with the onset of diabetes mellitus, unintentional weight loss, anemia, and diarrhea. Shortly thereafter, glossitis developed, along with a widespread pruritic rash that was recalcitrant to treatment with systemic and topical steroids. At the time of her referral to a dermatologist, her trunk and extremities were covered with gyrate, dusky tan-pink and bright pink-red plaques with exfoliative, hemorrhagic, and varnishlike scales; these did not affect the perianal area, hands, or feet. Skin biopsy revealed broad zones of confluent parakeratosis, an edematous dermis with a mixed infiltrate of lymphocytes, histiocytes, and occasional eosinophils. Immunofluorescence findings were negative. Subsequent studies indicate a markedly elevated fasting glucagon level and low serum amino acid and essential fatty acid levels. What are the diagnosis and most appropriate treatment?

Hint
CT scans revealed 2 masses in the pancreas (not shown).

 

 

 

 

Answer
Necrolytic migratory erythema: This patient's rash is consistent with necrolytic migratory erythema (NME), as part of the glucagonoma syndrome. Initial treatment with octreotide 200 mcg 3 times a day resulted in rapid symptomatic relief and resolution of her rash. She then underwent total pancreatectomy with the removal of regional metastases.

Glucagonoma syndrome consists of a glucagon-secreting tumor, diabetes mellitus, NME, anemia, hypoaminoaciduria, and weight loss. NME is often the most specific and readily diagnosable component of this syndrome and has been shown to be the presenting complaint in as many as two thirds of cases. The typical rash of NME appears as erythematous patches and plaques that develop flaccid vesicles or bullae, which later break resulting in denudation and crust formation. The differential diagnosis includes eczema, psoriasis, impetigo, acrodermatitis enteropathica (an eruption secondary to zinc deficiency), subcorneal pustular dermatosis, and autoimmune blistering diseases. The rash does not typically mirror glucagon levels and has a waxing-and-waning course with cycles lasting 7-14 days.

The key to the diagnosis in this patient was the simultaneous onset of rash and diabetes mellitus. NME most commonly occurs during the fifth or sixth decades of life. Glucagon levels cannot be checked in every patient in this age group who has a new onset of diabetes mellitus; however, the abrupt occurrence of recalcitrant new rash and diabetes mellitus should prompt testing of fasting glucagon levels. Early diagnosis of glucagonoma syndrome is key to survival because metastatic disease is often present when the diagnosis is made. NME with normal glucagon levels has also been reported in the setting of cystic fibrosis, pancreatitis, and celiac sprue.

For more information on glucagonoma syndrome, please see the eMedicine articles Glucagonoma Syndrome and Glucagonoma.