eMedicine Specialties > Dermatology > Internal Medicine

Necrolytic Acral Erythema

Author: Katherine Z Holcomb, MD, MPH,, Staff Physician, Department of Dermatology, National Naval Medical Center, National Capital Consortium Residency Program
Coauthor(s): Noah S Scheinfeld, MD, JD, FAAD, Assistant Clinical Professor, Department of Dermatology, Columbia University; Consulting Staff, Department of Dermatology, St Luke's Roosevelt Hospital Center, Beth Israel Medical Center, New York Eye and Ear Infirmary; Private Practice
Contributor Information and Disclosures

Updated: Jan 8, 2010

Introduction

Background

Necrolytic acral erythema (NAE) was first described in 1996 by physicians in Egypt, M. El Darouti and M. Abu El Ela.¹ Necrolytic acral erythema manifests as well-circumscribed, dusky erythematous plaques with adherent scale. While the plaques are psoriasiform, they do not manifest an Auspitz sign as would be seen with psoriasis. Patients with active necrolytic acral erythema report burning or pruritus. It is limited to an acral distribution and, in most cases, is associated with hepatitis C infection.^2,3 Several cases of necrolytic acral erythema have occurred in patients without hepatitis C.⁴ This suggests that necrolytic acral erythema might be a result of zinc dysregulation, rather than a result of hepatitis C infection itself.

Authors debate whether necrolytic acral erythema is a distinct entity or a subtype of necrolytic migratory erythema. However, the distinct appearance and usual coincidence with hepatitis C infections suggests that it is a unique entity.

Pathophysiology

The pathophysiology of this condition is uncertain. Proposed theories for the cause of necrolytic acral erythema describe alterations in some metabolic factor, many of which are seen in other necrolytic erythemas, including necrolytic migratory erythema, pellagra, essential fatty acid and biotin deficiency, and acrodermatitis enteropathica. The hypothesized causes for the metabolic alteration include hypoalbuminemia, hypoaminoacidemia, low zinc level, increased glucagon, liver dysfunction, or diabetes. Only hepatitis C is universally present in all persons with necrolytic acral erythema.

An odd fact is that no cases of necrolytic acral erythema have been reported in Japan, which has a high seroprevalence rate of hepatitis C.

Frequency

United States

Only 2 cases of necrolytic acral erythema have been described in the United States to date, but the condition is likely more common than the case reports suggest.

International

Forty-two cases of necrolytic acral erythema have been described internationally, mostly in Egypt. El-Ghandour et al⁵ in Egypt described a series of 23 patients (mean age, 41.7 ±11.5 y; male-to-female ratio, 10:13) with clinical features consistent with necrolytic acral erythema examined over a 3-year period. Most necrolytic acral erythema patients were adults (91.3%), and the skin lesions were predominantly chronic (78.3%), with the dorsa of the toes and/or feet affected in all cases.

Mortality/Morbidity

Necrolytic acral erythema has no known directly associated morbidly or mortality. Rather, the morbidity and mortality are related to the primary illness, hepatitis C.

Race

Most cases of necrolytic acral erythema have been reported in Egyptians. No cases have been reported in whites.

Sex

To date, no sex predisposition is reported for necrolytic acral erythema.

Age

The ages of the patients with necrolytic acral erythema have ranged from 11-60 years, but the onset typically occurs between 35-55 years.

Clinical

History

• Patients with necrolytic acral erythema present with a 1-month to 2-year history of a rash on the dorsum of the feet, which may or may not also involve the hands. In many cases, it has been unresponsive to topical steroids.
• Patients do not necessarily give a history of hepatitis C. Necrolytic acral erythema may be the presenting sign.
• Patients may report a burning sensation, especially when walking or standing. Sometimes, necrolytic acral erythema lesions are pruritic.
• The most common area of origination of the rash is the dorsal aspect of the great toe. It also occurs on the shins.
• In 43 of 44 reported cases, necrolytic acral erythema did not affect the palms or soles, the nail bed, nail plate, or mucous membranes.
• Williams⁶ reported a case of necrolytic acral erythema in an adolescent boy with a history of infection with hepatitis C virus; he had hepatic fibrosis, hypertension, and thrombocytopenia. The patient developed a pruritic eruption on his face, trunk, genitals, and extremities, and the eruption had a predilection for bony prominences. This patient did not respond to topical steroids, antihistamines, topical barrier repair creams, narrow-band UV-B therapy, or tar baths. A skin biopsy specimen demonstrated a nonspecific psoriasiform dermatitis consistent with necrolytic acral erythema. Hepatitis C virus RNA polymerase chain reaction studies showed 974,000 IU/mL (<50) and hepatitis C virus RNA genotype 1b.
• Janjua⁷ noted a 45-year-old man who developed well-defined erythematous hyperpigmented keratotic pruritic plaques on the dorsa of his feet and the lateral aspect of his ankles; he was determined to have necrolytic acral erythema.

Physical

• Dusky, red erythematous plaques are present bilaterally on the dorsum of the feet and toes. These may extend around to the skin overlying the Achilles tendon and up the lower leg, as depicted in the image below.
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  Plaque of necrolytic acral erythema on the ankle of a male.

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  Plaque of necrolytic acral erythema on the ankle of a male.

• The dorsum of the hands may or may not be involved.
• The lesions are clearly demarcated from uninvolved skin by a dark red border.
• The surface may be scaly, eroded, or velvety. Thick hyperkeratosis is sometimes present.
• Active lesions often include flaccid blisters.
• Edema may or may not be present.
• Abdallah et al⁸ describe stages of the lesions: 
  1. Initial stage: Erythematous papules or plaque with scale are present and have a dusky or eroded center.
  2. Fully developed stage: A confluence of papules and plaques with sharply defined margins and adherent scale develops. Increased hyperpigmentation and decreased redness may be present. Lesions may be lichenified. Pustules also may occur at this stage.
  3. Late stage: Thinning of lesions occurs, with continued hyperpigmentation. Demarcation continues, followed by spontaneous relapse and remission.
• As a general rule, necrolytic acral erythema does not affect the palms or soles, the nail bed, nail plate, or mucous membranes. Hivnor et al⁹ reported a single case in which the plaques extended proximally to the thighs. This patient also had hyperkeratosis of the palms and soles and involvement of the face. While multiple biopsy specimens confirmed necrolytic acral erythema histologically, it is not clear whether these biopsy specimens were taken from the typical locations of necrolytic acral erythema or if the palms and soles were also included in the biopsy specimen.
• Other disorders that can be seen in persons with hepatitis C should be considered as possible epiphenomena. These include the following: 
  • Lichen planus
  • Porphyria cutanea tarda
  • Palpable purpura/leukocytoclastic vasculitis
  • Spider telangiectasias
  • Vitiligo
  • Polyarteritis nodosa
  • Erythema multiforme
  • Urticaria
  • Erythema nodosum

Causes

The cause is uncertain, but a metabolic alteration due to hepatocellular degeneration from hepatitis C infection is proposed. Many hypotheses describe deficiencies similar to those of the other necrolytic erythemas; histological features are similar among necrolytic acral erythema and other nutrient deficiencies.

• el Darouti and Abu El Ela¹ suggested that the increased levels of glucagon seen in persons with liver disease allow for "potentiation" of arachidonic acid after trauma.
• High glucagon levels alone may allow for greater arachidonic acid potentiation, which may induce inflammatory changes and necrosis in the epidermis.
• Low amino acid levels may lead to epidermal protein depletion and necrolysis.
• Low albumin levels have also been postulated as causative. Albumin sequesters fatty acids and helps regulate prostaglandin levels. High levels of prostaglandins as a result of low levels of albumin may induce inflammation.
• Low zinc levels have also been proposed as a cause. Because albumin is the main carrier of zinc in plasma, these 2 may be interrelated.
• Diabetic microangiopathy also may play a role; 4 of 5 necrolytic acral erythema patients described by Nofal et al¹⁰ also had diabetes.

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