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Necrolytic Acral Erythema
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.
- 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:
- Initial stage: Erythematous papules or plaque with scale are present and have a dusky or eroded center.
- 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.
- 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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Overview: Necrolytic Acral Erythema |
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References
el Darouti M, Abu el Ela M. Necrolytic acral erythema: a cutaneous marker of viral hepatitis C. Int J Dermatol. Apr 1996;35(4):252-6. [Medline].
Abdallah MA, Ghozzi MY, Monib HA, et al. Necrolytic acral erythema: a cutaneous sign of hepatitis C virus infection. J Am Acad Dermatol. Aug 2005;53(2):247-51. [Medline].
Khanna VJ, Shieh S, Benjamin J, et al. Necrolytic acral erythema associated with hepatitis C: effective treatment with interferon alfa and zinc. Arch Dermatol. Jun 2000;136(6):755-7. [Medline].
Wu YH, Tu ME, Lee CS, Lin YC. Necrolytic acral erythema without hepatitis C infection. J Cutan Pathol. Mar 2009;36(3):355-8. [Medline].
El-Ghandour TM, Sakr MA, El-Sebai H, El-Gammal TF, El-Sayed MH. Necrolytic acral erythema in Egyptian patients with hepatitis C virus infection. J Gastroenterol Hepatol. Jul 2006;21(7):1200-6. [Medline].
Williams J. Necrolytic acral erythema. DermAtlas. Available at http://dermatlas.med.jhmi.edu/derm/result.cfm?Diagnosis=178630456. Accessed January 25, 2007.
Janjua SA. Necrolytic acral erythema. DermAtlas. Available at http://dermatlas.med.jhmi.edu/derm/result.cfm?Diagnosis=178630456. Accessed January 25, 2007.
Abdallah MA, Ghozzi MY, Monib HA, et al. Histological study of necrolytic acral erythema. J Ark Med Soc. Apr 2004;100(10):354-5. [Medline].
Hivnor CM, Yan AC, Junkins-Hopkins JM, Honig PJ. Necrolytic acral erythema: response to combination therapy with interferon and ribavirin. J Am Acad Dermatol. May 2004;50(5 Suppl):S121-4. [Medline].
Nofal AA, Nofal E, Attwa E, El-Assar O, Assaf M. Necrolytic acral erythema: a variant of necrolytic migratory erythema or a distinct entity?. Int J Dermatol. Nov 2005;44(11):916-21. [Medline].
Najarian DJ, Lefkowitz I, Balfour E, Pappert AS, Rao BK. Zinc deficiency associated with necrolytic acral erythema. J Am Acad Dermatol. Nov 2006;55(5 Suppl):S108-10. [Medline].
Najarian DJ, Najarian JS, Rao BK, Pappert AS. Hypozincemia and hyperzincuria associated with necrolytic acral erythema. Int J Dermatol. Jul 2008;47(7):709-11. [Medline].
Bentley D, Andea A, Holzer A, Elewski B. Lack of classic histology should not prevent diagnosis of necrolytic acral erythema. J Am Acad Dermatol. Mar 2009;60(3):504-7. [Medline].
Abdallah MA, Hull C, Horn TD. Necrolytic acral erythema: a patient from the United States successfully treated with oral zinc. Arch Dermatol. Jan 2005;141(1):85-7. [Medline].
de Carvalho Fantini B, Matsumoto FY, Arnone M, Sotto MN, Junior WB. Necrolytic acral erythema successfully treated with oral zinc. Int J Dermatol. Aug 2008;47(8):872-3. [Medline].
Manzur A, Siddiqui AH. Necrolytic acral erythema: successful treatment with topical tacrolimus ointment. Int J Dermatol. Oct 2008;47(10):1073-5. [Medline].
Marinkovich MP, Botella R, Datloff J, Sangueza OP. Necrolytic migratory erythema without glucagonoma in patients with liver disease. J Am Acad Dermatol. Apr 1995;32(4):604-9. [Medline].
Pujol RM, Wang CY, el-Azhary RA, Su WP, Gibson LE, Schroeter AL. Necrolytic migratory erythema: clinicopathologic study of 13 cases. Int J Dermatol. Jan 2004;43(1):12-8. [Medline].
van Beek AP, de Haas ER, van Vloten WA, Lips CJ, Roijers JF, Canninga-van Dijk MR. The glucagonoma syndrome and necrolytic migratory erythema: a clinical review. Eur J Endocrinol. Nov 2004;151(5):531-7. [Medline].
Further Reading
Keywords
necrolytic acral erythema, NAE, acral necrolytic migratory erythema, NME, hepatitis C virus, hepatitis C infection, hepatitis, necrolytic migratory erythema


Overview: Necrolytic Acral Erythema