Necrolytic acral erythema

Management Strategy

Some have categorized the evolution of NAE into three distinct stages. The initial stage consists of a small (2–3 mm), erythematous papule that grows in surface area and thickness to become covered in scale. The center of the papule may become dusky or develop an erosion. The fully developed stage consists of increasing surface area and confluence of the initial stage lesions, leading to sharply demarcated erythematous lichenified plaques with overlying scale. Thin crust, vesicles, pustules, and weeping may also be seen in this stage. The late stage is characterized by thinning and hyperpigmentation of previously developed lesions, followed by spontaneous relapse and remission. The lesions of NAE are often locally pruritic, although in some cases, the pruritus can be generalized. Other patients have complained the lesions cause aching or burning pain.

Although the exact pathogenesis of NAE is not known, infection with hepatitis C seems to have an essential role in its development. The lack of NAE lesions in patients with other cirrhotic conditions, such as alcoholic hepatitis or hepatitis B infection, excludes chronic liver damage as the sole cause. Attempts to identify hepatitis C viral particles or RNA in NAE biopsies using electron microscopy and reverse transcription polymerase chain reaction (RT-PCR) have not been successful. Reduced amino acid levels, elevated glucagon levels, reduced fatty acid levels, reduced serum zinc, and reduced epidermal zinc have all been implicated in NAE and may be related to HCV-induced metabolic alterations. Zinc deficiency, especially, has been suggested as a pathogenic factor given the responsiveness of some cases of NAE to oral zinc sulfate. Although many patients with NAE who respond to oral zinc have normal serum zinc levels, some have postulated that these patients may have low cutaneous zinc levels. The role of zinc in the pathogenesis of NAE remains unclear. Because zinc is believed to be antiapoptotic, some have postulated that its deficiency may lead to epidermal necrolysis. Zinc deficiency may also impair the transport of essential nutrients like vitamin A to the epidermis. Because not all patients with NAE are responsive to oral zinc supplementation, it is likely the etiology of NAE is multifactorial.

In one study, 87% of patients diagnosed with NAE were unaware of their underlying HCV infection. Hence, identification of NAE suggests the need to test for HCV.

Early NAE may present with vesicular lesions on the dorsal hands or feet that may be confused with acute eczematous reactions, contact dermatitis, or stasis changes when it is limited to the feet and/or legs. Chronic NAE may mimic lichen simplex chronicus. The necrolytic erythemas include necrolytic migratory erythema, acrodermatitis enteropathica, pellagra, and NAE. Although these entities may all share some clinical and histologic features, they can be distinguished based on cutaneous distribution and underlying biochemical abnormalities. Necrolytic migratory erythema presents with elevated glucagon levels, whereas acrodermatitis enteropathica presents with depressed zinc levels, and pellagra is associated with niacin deficiency. NAE may also be distinguished based on its association with HCV and acral distribution.

On histology, NAE demonstrates psoriasiform hyperplasia, acanthosis, papillomatosis, and parakeratosis. Vascular ectasia can be seen within the dermal papillae, along with pigment incontinence. Most cases show a superficial, patchy, dermal, perivascular lymphocytic and neutrophilic infiltrate with extension into the epidermis, and necrotic keratinocytes in the superficial epidermis. In the absence of necrotic keratinocytes, NAE can be easily confused with psoriasis, histologically. Because NAE lacks pathognomonic histology, a high index of suspicion and clinical–pathologic correlation is required for diagnosis.

In patients who may have NAE, a hepatitis panel and liver function tests can help to clarify the diagnosis. Other tests that may distinguish NAE from entities in the differential diagnosis include serum albumin, total protein, amino acids, zinc, biotin, and glucagon levels.