Necrotizing Migratory Erythema: Causes, Signs, and Care

Necrotizing migratory erythema is a rare skin condition often signaling underlying systemic disease. Recognizing it is crucial, as it can indicate metabolic disturbances or malignancies requiring medical attention.

Clinical Presentation

Necrotizing migratory erythema (NME) presents as erythematous, annular plaques with central clearing and peripheral expansion, often forming serpiginous or polycyclic patterns. These lesions typically appear on the lower abdomen, perineum, buttocks, and proximal extremities but may spread over time. Superficial necrosis can lead to erosions or crusting, causing discomfort and increasing the risk of secondary infections. Many patients report pruritus or a burning sensation before visible skin changes, complicating diagnosis.

Lesions evolve in a waxing and waning manner, with new areas emerging while older ones resolve, sometimes leaving post-inflammatory hyperpigmentation. This fluctuating course may delay recognition of the underlying pathology. In some cases, vesiculation or bullae formation occurs, adding to diagnostic complexity. The presence of superficial epidermal necrosis with a dusky or violaceous hue suggests ongoing tissue damage.

Systemic symptoms such as weight loss, fatigue, and gastrointestinal disturbances frequently accompany the skin findings. These broader manifestations often indicate metabolic derangements, particularly in cases linked to glucagonoma syndrome. The chronic nature of the lesions, combined with systemic signs, should prompt further investigation, as delayed diagnosis can worsen metabolic complications.

Pathophysiology

Necrotizing migratory erythema (NME) is primarily associated with metabolic disturbances, most notably glucagonoma syndrome. This rare neuroendocrine tumor of the pancreatic alpha cells leads to excessive glucagon secretion, disrupting metabolic homeostasis. Glucagon promotes gluconeogenesis and lipolysis while inhibiting glycogen synthesis, creating a hypercatabolic state. This results in amino acid depletion, hypoalbuminemia, and oxidative stress, compromising skin integrity and contributing to NME lesions.

Amino acid deficiencies, particularly in essential amino acids like cysteine, tryptophan, and lysine, impair keratinocyte function and disrupt epidermal barrier maintenance. This weakens structural proteins necessary for skin regeneration, increasing susceptibility to necrosis and delayed wound healing. Hypoalbuminemia exacerbates tissue damage by reducing oncotic pressure, leading to interstitial edema that further impairs cutaneous circulation and promotes ischemic stress.

Zinc and other trace element deficiencies also play a role. Patients with glucagonoma often exhibit hypozincemia, which affects enzymatic functions necessary for skin repair and immune defense. Zinc-dependent metalloproteinases are critical for matrix remodeling and epidermal turnover, and their dysfunction leads to prolonged inflammation and defective barrier restoration. Combined with the catabolic effects of glucagon, this accelerates the formation of erythematous plaques with central clearing.

Microvascular changes contribute to NME progression. Chronic hyperglucagonemia induces endothelial dysfunction, reducing nitric oxide bioavailability and impairing vasodilation. This leads to localized ischemia, promoting dusky, violaceous plaques that undergo necrosis. The combination of endothelial damage, amino acid depletion, and metabolic stress perpetuates the relapsing-remitting pattern of lesions.

Associated Conditions

Necrotizing migratory erythema (NME) is strongly linked to glucagonoma syndrome, a rare pancreatic neuroendocrine tumor that secretes excessive glucagon. Patients with glucagonoma frequently present with diabetes mellitus, weight loss, anemia, and thromboembolic complications. NME may appear months or even years before tumor diagnosis, making it a valuable early marker.

Beyond glucagonoma, other metabolic and nutritional deficiencies can contribute to NME-like eruptions. Hypoalbuminemia and amino acid deficiencies impair skin repair, increasing susceptibility to necrosis. Zinc deficiency, common in malabsorptive conditions like celiac disease or chronic pancreatitis, further exacerbates cutaneous manifestations by impairing wound healing. NME-like lesions have also been reported in cirrhosis, where hepatic dysfunction leads to metabolic imbalances that mimic glucagon excess.

Paraneoplastic syndromes linked to non-pancreatic malignancies can also resemble NME. Certain neuroendocrine tumors, such as bronchial carcinoids and gastrointestinal neoplasms, secrete bioactive peptides that disrupt metabolic pathways, leading to similar skin findings. Additionally, hematologic malignancies like multiple myeloma can contribute to amino acid depletion and systemic inflammation, triggering skin changes that mimic NME. These cases highlight the need for thorough systemic evaluation when NME-like lesions are present.

Diagnostic Methods

Diagnosing necrotizing migratory erythema (NME) requires clinical evaluation alongside laboratory and imaging studies. The characteristic annular or serpiginous lesions with superficial necrosis provide strong diagnostic clues, but ruling out other conditions is essential. A thorough patient history, including unexplained weight loss, glucose intolerance, and gastrointestinal symptoms, can raise suspicion for an underlying metabolic disorder. Examining lesion distribution and progression helps differentiate NME from other inflammatory dermatoses.

Laboratory tests play a key role, particularly serum glucagon levels, which are elevated in glucagonoma. Plasma glucagon concentrations above 500 pg/mL strongly suggest a glucagon-secreting tumor, though levels may vary with tumor burden. Additional metabolic panels often reveal hypoalbuminemia, normocytic anemia, and electrolyte imbalances. Zinc and amino acid levels should also be assessed, as deficiencies can exacerbate skin manifestations.

Histopathological examination of skin biopsies can support diagnosis by revealing epidermal necrosis, parakeratosis, and pallor of the upper epidermis. Superficial perivascular inflammation, often with neutrophilic infiltration, may be present but is not specific to NME. Imaging studies, such as contrast-enhanced CT or MRI of the pancreas, are typically performed to locate a glucagonoma. Functional imaging with somatostatin receptor-based modalities, such as Ga-68 DOTATATE PET/CT, offers superior sensitivity in detecting neuroendocrine tumors and assessing metastatic spread.

Disease Progression Patterns

The course of necrotizing migratory erythema (NME) is unpredictable, with lesions demonstrating cycles of resolution and recurrence. Early lesions appear as erythematous plaques with annular or serpiginous configurations, expanding peripherally while central clearing occurs. Over time, lesions may coalesce into polycyclic patterns. The necrotic component develops in later stages as metabolic imbalances impair tissue repair, leading to superficial erosions, crusting, and desquamation. Some lesions persist for weeks before resolving, often leaving post-inflammatory hyperpigmentation.

Without intervention, NME worsens, reflecting the progression of the underlying metabolic disorder. In glucagonoma-related cases, persistent lesions indicate ongoing tumor activity, and worsening skin findings often parallel tumor growth or metastasis. Systemic symptoms such as weight loss and glucose intolerance can exacerbate cutaneous findings, as prolonged catabolic states further impair skin regeneration. In undiagnosed glucagonoma, NME may fluctuate in severity, with temporary improvements due to dietary changes or metabolic shifts. However, without targeted treatment, the disease remains chronic and relapsing, with flare-ups becoming more frequent.

Similar Dermatological Conditions

Several skin disorders resemble NME, making differential diagnosis essential. Erythema gyratum repens, a paraneoplastic dermatosis, shares annular and serpiginous patterns but exhibits a more pronounced wood-grain appearance with rapid lesion migration. Unlike NME, it lacks necrotic and erosive features and is often linked to internal malignancies.

Necrolytic acral erythema, associated with hepatitis C, presents as erythematous plaques that progress to scaling and hyperkeratosis, primarily affecting the dorsal hands and feet. While histopathological similarities exist, necrolytic acral erythema is distinctly linked to zinc deficiency and responds well to supplementation, whereas NME requires broader metabolic correction.

Pemphigus foliaceus, an autoimmune blistering disorder, can be confused with NME due to its superficial erosions and crusted plaques. However, its distribution favors seborrheic regions such as the face, chest, and upper back. Direct immunofluorescence studies revealing intercellular IgG deposition help distinguish it from NME. Given these overlapping presentations, careful clinical correlation, laboratory testing, and histopathological examination are necessary for accurate diagnosis and management.