Dermatology MCQ - Inflammatory Dermatoses - Necrolytic migratory erythema

A 55-year-old woman presents with a several-month history of a painful, blistering rash that predominantly involves the perioral area, lower abdomen, and groin. The eruption is characterized by erythematous patches with superficial erosions, crusting, and peripheral scaling. She also reports a 15-pound weight loss, new-onset diabetes mellitus, and painful glossitis. The most specific laboratory test to confirm the underlying diagnosis is:

A. Fasting blood glucose and HbA1c
B. Serum glucagon level
C. Anti-desmoglein 3 antibody
D. Serum zinc level
E. Tissue transglutaminase (tTG) IgA antibody

Correct Answer: B. Serum glucagon level

Answer & Explanation

Explanation:

The constellation of symptoms is classic for the Glucagonoma Syndrome, of which Necrolytic Migratory Erythema (NME) is the hallmark dermatologic manifestation.

• Key Diagnostic Clues:

  • Rash (NME): A painful, intertriginous, and periorificial rash with a characteristic cycle of erythema, blistering, erosion, and crusting.

  • Systemic Findings: The triad of weight loss, new-onset diabetes mellitus, and glossitis (or stomatitis) is highly suggestive.

  • Pathophysiology: This is a paraneoplastic syndrome caused by a glucagon-secreting pancreatic alpha-cell tumor (glucagonoma).

Measuring the serum glucagon level is the most specific confirmatory test. Levels are typically dramatically elevated (>500 pg/mL, often >1000 pg/mL).

The other options are incorrect:

• A. Fasting blood glucose and HbA1c: These would confirm the diagnosis of diabetes mellitus, which is a component of the syndrome, but they do not identify the underlying glucagonoma as the cause.

• C. Anti-desmoglein 3 antibody: This is the serologic marker for pemphigus vulgaris, which can also present with oral erosions and blisters. However, pemphigus does not cause the characteristic migratory rash, weight loss, or glossitis seen in NME.

• D. Serum zinc level: A zinc deficiency can cause acrodermatitis enteropathica, which shares some features with NME (periorificial and acral dermatitis, diarrhea). However, it does not typically present with the same severe, migratory pattern, new-onset diabetes, or the specific distribution described. Zinc levels are often low in NME due to the catabolic state, but this is a secondary finding, not the primary cause.

• E. Tissue transglutaminase (tTG) IgA antibody: This is the primary serologic test for celiac disease, which can present with a dermatitis herpetiformis. Dermatitis herpetiformis is intensely pruritic, not painful, and consists of symmetric, grouped vesicles on extensor surfaces, not a migratory, erosive rash in intertriginous areas.

Key Associations for Necrolytic Migratory Erythema

• Pathophysiology: Caused by a glucagon-secreting pancreatic neuroendocrine tumor. The exact mechanism of the rash is multifactorial, thought to involve hyperglucagonemia, hypoaminoacidemia, zinc deficiency, and hepatic dysfunction, leading to epidermal protein deficiency and necrolysis.

• Clinical Presentation: The rash has a characteristic cyclic and migratory pattern. Lesions begin as erythematous patches that develop superficial flaccid blisters and pustules, which rupture to form erosions and crusts with a collarette of scale. It has a predilection for the perioral area, groin, perineum, and lower abdomen.

• Histopathology: The hallmark is upper epidermal necrolysis (pallor and necrosis of the upper layers of the epidermis) with associated confluent parakeratosis and an underlying superficial dermal inflammatory infiltrate. The histology can be subtle and requires correlation with clinical findings.

• Differential Diagnosis: Includes pemphigus foliaceus, seborrheic dermatitis, psoriasis, acrodermatitis enteropathica, and pellagra.

• Prognosis: Glucagonomas are typically malignant, with metastases often present at diagnosis (commonly to the liver). The prognosis is variable but has improved with advanced surgical techniques and somatostatin analog therapy.

• Management:

  1. Localize the Tumor: Once the glucagon level is confirmed, imaging with CT or MRI of the abdomen and somatostatin receptor scintigraphy (Octreoscan) is performed.

  2. Surgical Resection: This is the only curative option if the tumor is localized.

  3. Symptomatic Control: Long-acting somatostatin analogs (e.g., octreotide, lanreotide) are highly effective for controlling both the skin eruption and other systemic symptoms by suppressing glucagon secretion.

  4. Supportive Care: Nutritional support, amino acid and zinc supplementation, and diabetes management are crucial.