Necrolytic Acral Erythema

Necrolytic acral erythema is a skin disease that appears in the toes and the feet. It was first described in the literature in 1996. It is known as the cutaneous marker for hepatitis C infection and is strongly linked with it. The majority of recorded cases, which have an equal sex frequency and a mean onset age of 40–45 years (range 11–78 years), have been in people with skin of color, including Asians and Africans.


Necrolytic acral erythema is thought to be multifactorial, possibly due to low blood levels of albumin, glucagon, and amino acids caused by liver failure, dietary deficiencies (particularly zinc insufficiency), and hereditary factors.

The most common cause is hepatitis C infection, where a study conducted in the USA suggested that necrolytic acral erythema was observed in 1-2% of patients with chronic hepatitis C. The second most common association was found to be zinc deficiency occurring with various other disorders including coeliac disease and Crohn’s disease. It is important to note that for the hepatitis C virus to replicate, zinc is a necessary cofactor. 

Interestingly, the prevalence of chronic hepatitis C infection is high in Japan, in contrast, there are no reported cases of necrolytic acral erythema. This could be a result of genetic predisposition or the prevalent hepatitis C genotypes in that group.

Clinical features:

Usually, the tops of the toes and feet are affected by necrotic acral erythema. The skin lesions are painful most of the time, although they might also occasionally be itchy or burning. 

Acute cases present as erythematous lesions with a margin of erosions or flaccid bullae. 

Chronic cases can be divided into three phases:

  • The initial phase presents with ducky scaly papules or plaques. 
  • The well-developed phase presents with large hyperpigmented well-demarcated papules and plaques. 
  • The late phase presents with thin psoriasiform hyperpigmented lesion with a well-defined dark red rim.

Dermoscopy shows the following findings:

  • Central white and brown peripheral globules. 
  • Irregular red spot in the center. 
  • Brown background.
  • Dull white scale.


  • Laboratory investigations include hepatitis C serology, liver function tests, and serum zinc.
  •  A skin biopsy is used to confirm the diagnosis and it shows inflammatory infiltrate, hyperkeratosis, parakeratosis, epidermal spongiosis, and focal necrosis. 

Differential diagnosis:

Necrolytic migratory erythema is one of the most important differential diagnoses, as it has similar skin biopsy results. Other differentials include psoriasis, pellagra, and biotin-responsive dermatoses. 


Treat the underlying causes mostly hepatitis C with combination therapy with interferon and ribavirin, and oral zinc supplements (220 mg BID) which could enhance the effects of hepatitis C treatment. 


Complications of hepatitis C due to missing the diagnosis. Other complications include lichenification and fissuring. 


The disease follows a relapsing-remission course, with appropriate treatment it can resolve, however, recurrence could be observed if treatment is stopped. 



Written by:

Mohammed Alahmadi, Medical Student. 

Revised by:

Maee Barakeh, Medical Student. 




Andrews’ Diseases of The Skin, Clinical Dermatology 

Dermatology by Bolognia