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World J Hepatol 2019 Feb;11(2):226-233

Division of Liver Diseases, Icahn School of Medicine at Mount Sinai, New York, NY 10029, United States.

Background: Necrolytic acral erythema (NAE) is a rare dermatological disorder, which is associated with hepatitis C virus (HCV) infection or zinc deficiency. It is characterized by erythematous or violaceous lesions occurring primarily in the lower extremities. The treatment includes systemic steroids and oral zinc supplementation. Read More

Br J Dermatol 2018 Aug;179(2):e88

Department of Dermatology, Peking Union Medical College Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College, No. 1 Shuaifuyuan, Dongcheng District, Beijing, China.

Dig Liver Dis 2018 Aug 12;50(8):854. Epub 2018 Mar 12.

Department of Dermatology, Venereology and Leprology, Postgraduate Institute of Medical Education and Research, Chandigarh 160012, India. Electronic address:

Clin Liver Dis 2017 08 25;21(3):555-564. Epub 2017 Apr 25.

Betty and Guy Beatty Center for Integrated Research, Inova Health System, Inova Fairfax Hospital, Claude Moore Health Education and Research Building, 3rd Floor, 3300 Gallows Road, Falls Church, VA 22042, USA; Department of Medicine, Center for Liver Disease, Inova Fairfax Hospital, Claude Moore Health Education and Research Building, 3rd Floor, 3300 Gallows Road, Falls Church, VA 22042, USA. Electronic address:

Chronic hepatitis C virus (HCV) infection is associated with various extrahepatic manifestations, including dermatologic involvement mostly caused by immune complexes. Mixed cryoglobulinemia has a strong relationship with HCV with 95% of these patients being infected with HCV. Lichen planus is a disease of the squamous epithelium and may affect any part of the skin, with 4% to 24% of patients with lichen planus reported to have chronic HCV infection. Read More

Case Rep Dermatol 2017 Jan-Apr;9(1):69-73. Epub 2017 Mar 17.

Division of Dermatology, Faculty of Medicine, Ramathibodi Hospital, Mahidol University, Bangkok, Thailand.

Necrolytic acral erythema (NAE) is a distinctive skin disorder. The exact cause and pathogenesis is still unclear. Most studies report an association of NAE with hepatitis C virus (HCV) infection. Read More

J Eur Acad Dermatol Venereol 2017 Aug 29;31(8):1260-1270. Epub 2017 Mar 29.

Ronald O. Perelman Department of Dermatology, New York University School of Medicine, New York, NY, USA.

New all-oral direct-acting antivirals (DAA) have changed the hepatitis C virus (HCV) treatment landscape. Given that dermatologists frequently encounter HCV-infected patients, knowledge of the current treatment options and their utility in treating HCV-associated dermatologic disorders is important. In addition to highlighting the new treatment options, we review four classically HCV-associated dermatologic disorders - mixed cryoglobulinaemia (MC), lichen planus (LP), porphyria cutanea tarda (PCT) and necrolytic acral erythema (NAE) - and examine the role for all-oral direct-acting antiviral (DAA) regimens in their treatment. Read More

Clin Dermatol 2017 Jan - Feb;35(1):40-49. Epub 2016 Sep 10.

Emeritus Professor of Gazi University, Faculty of Medicine, Department of Dermatology, Beşevler, Ankara, Turkey.

Viruses are considered intracellular obligates with a nucleic acid RNA or DNA. They have the ability to encode proteins involved in viral replication and production of the protective coat within the host cells but require host cell ribosomes and mitochondria for translation. The members of the families Herpesviridae, Poxviridae, Papovaviridae, and Picornaviridae are the most commonly known agents for cutaneous viral diseases, but other virus families, such as Adenoviridae, Togaviridae, Parvoviridae, Paramyxoviridae, Flaviviridae, and Hepadnaviridae, can also infect the skin. Read More

An Bras Dermatol 2016 Sep-Oct;91(5):649-651

Universidade Federal de São Paulo (Unifesp) - São Paulo (SP), Brazil.

Necrolytic acral erythema is a rare skin disease associated with hepatitis C virus infection. We report a case of a 31-year-old woman with hepatitis C virus infection and decreased zinc serum level. Physical examination revealed scaly, lichenified plaques, well-demarcated with an erythematous peripheral rim located on the lower limbs. Read More

Indian Dermatol Online J 2016 Jul-Aug;7(4):304-7

Department of Dermatology, Venereology and Leprosy, Shri BM Patil Medical College, Hospital and Research Centre, BLDE University, Bijapur, Karnataka, India.

Necrolytic acral erythema (NAE) is a newly described entity, seen in patients infected with hepatitis C virus. It is characterized by its distinguishing acral distribution, psoriasiform skin eruption and histological features. Its etiopathogenesis is not fully understood though hypo amino academia, hyperglucagonemia and zinc deficiency are considered as probable causes. Read More

Arch Biochem Biophys 2016 Dec 7;611:113-119. Epub 2016 Jun 7.

Department of Dermatology, Faculty of Medicine, University of Yamanashi, Yamanashi, 409-3898, Japan.

Of all tissues, the skin has the third highest abundance of zinc in the body. In the skin, the zinc concentration is higher in the epidermis than in the dermis, owing to a zinc requirement for the active proliferation and differentiation of epidermal keratinocytes. Here we review the dynamics and functions of zinc in the skin as well as skin disorders associated with zinc deficiency, zinc finger domain-containing proteins, and zinc transporters. Read More

Int J Low Extrem Wounds 2016 Sep 5;15(3):260-2. Epub 2016 Jun 5.

Taipei Veterans General Hospital, Taipei, Taiwan National Yang-Ming University, Taipei, Taiwan.

Necrolytic acral erythema (NAE) is a recently recognized dermatosis almost exclusively associated with hepatitis C virus (HCV) infection, and closely related to zinc deficiency. We present the case of a 60-year-old man with a history of psoriasis and chronic HCV infection, who developed new lesions of NAE extending from previous elephantine psoriatic plaques on bilateral lower legs. According to previous reports, resolution of NAE has been successfully achieved by treatment of the underlying HCV infection, or the use of oral zinc therapy. Read More

Indian J Dermatol 2016 Jan-Feb;61(1):96-9

Department of Dermatology, Medical College and Hospital, Kolkata, India.

World J Hepatol 2015 Nov;7(27):2740-8

Simone Garcovich, Rodolfo Capizzi, Department of Dermatology, Policlinico A. Gemelli, Catholic University of Sacred Heart, 00168 Rome, Italy.

The association of chronic hepatitis C virus (HCV) infection with a wide spectrum of cutaneous manifestations has been widely reported in the literature, with varying strength of epidemiological association. Skin diseases which are certainly related with chronic HCV infection due to a strong epidemiological and pathogenetic association are mixed cryoglobulinemia, lichen planus and porphyria cutanea tarda. Chronic pruritus and necrolytic acral erythema are conditions that may share a possible association with HCV infection, while several immune-mediated inflammatory skin conditions, such as psoriasis, chronic urticaria and vitiligo, have been only anecdotally reported in the setting of chronic HCV infection. Read More

Am J Med 2015 Aug 8;128(8):e3-4. Epub 2015 Apr 8.

Department of General Internal Medicine, St. Michael's Hospital, Toronto, Ontario, Canada.

Indian J Dermatol 2015 Mar-Apr;60(2):136-41

Department of Dermatology, Institute of Post-Graduate Medical Education and Research (IPGMER), Kolkata, West Bengal, India.

Background: We are reporting a series of interesting cases, which presented to us with psoriasiform lesions distributed over the acral regions of the body. The cases are unusual because they were resistant to conventional treatment modalities like topical corticosteroids, tacrolimus and oral methotrexate but showed significant improvement on oral zinc therapy.

Materials And Methods: Ten patients with characteristic clinical features of distinctive hyperkeratotic plaque in the acral areas, who were resistant to treatment by different modalities including potent topical steroids and oral methotrexate, were included for detailed investigations. Read More

Dermatol Online J 2014 Nov 15;20(11). Epub 2014 Nov 15.

Florida State College of Medicine.

Necrolytic acral erythema (NAE) is a rare cutaneous sign of hepatitis C virus infection and has recently been linked to zinc deficiency. It presents as well-demarcated erythematous plaques in a sandal-like distribution on the dorsal feet with psoriasiform epidermal hyperplasia on histology. Our patient reported a 9-month history of progressive bilateral lower extremity erythema, swelling, erosions, and nail dystrophy that failed to improve despite multiple courses of antibiotics for presumed lower extremity cellulitis. Read More

Br J Dermatol 2014 Nov 24;171(5):1255-6. Epub 2014 Sep 24.

University of Montpellier I and Department of Dermatology, St Eloi Hospital, CHU Montpellier, Montpellier, France; Department of Pathology, Gui de Chauliac Hospital, CHU Montpellier, Montpellier, France.

Dermatol Online J 2013 Dec 16;19(12):20709. Epub 2013 Dec 16.

New York University School of Medicine.

Necrolytic acral erythema is a rare, cutaneous manifestation of hepatitis C virus infection that is characterized by erythematous, violaceous or dusky papules, blisters, and/or erosions in the early stages and by well-demarcated, hyperkeratotic, targetoid plaques with a peripheral rim of macular erythema, secondary lichenification and hyperpigmentation, and overlying fine micaceous or necrotic-appearing scale in the later stages. Because most topical modalities prove ineffective, treatment of the underlying viral infection or therapeutic zinc supplementation are required for clinical improvement. Read More

J Drugs Dermatol 2012 Nov;11(11):1370-1

Department of Dermatology, Virginia Commonwealth University Health System, Richmond, VA, USA.

Clin Dev Immunol 2012 5;2012:740138. Epub 2012 Aug 5.

The Lillian and Henry M. Stratton-Hans Popper Department of Pathology, Mount Sinai School of Medicine, New York, NY 10029, USA.

Cirrhosis and hepatocellular carcinoma are the prototypic complications of chronic hepatitis C virus infection in the liver. However, hepatitis C virus also affects a variety of other organs that may lead to significant morbidity and mortality. Extrahepatic manifestations of hepatitis C infection include a multitude of disease processes affecting the small vessels, skin, kidneys, salivary gland, eyes, thyroid, and immunologic system. Read More

J Am Acad Dermatol 2012 Nov 9;67(5):962-8. Epub 2012 Feb 9.

Department of Dermatology, Perelman School of Medicine at the University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.

Background: Chronic hepatitis C virus (HCV) infection is associated with necrolytic acral erythema (NAE). However, the prevalence of NAE among patients with HCV is unknown, and the clinical and histologic features have not been well defined.

Objective: We sought to determine the prevalence, overall clinical features, and cutaneous histopathological characteristics of patients with NAE. Read More

Cutis 2011 Oct;88(4):185-8

Thomas Jefferson University, Philadelphia, Pennsylvania, USA.

The necrolytic erythemas is a group of disorders with similar histologic and clinical features. The objective of this case report is to present a patient with features of both necrolytic migratory erythema (NME) and necrolytic acral erythema (NAE). These 2 entities appear more likely to be on a spectrum caused by the same underlying process of abnormal liver function and glucagon metabolism. Read More

Pediatr Dermatol 2011 Nov-Dec;28(6):701-6. Epub 2011 Oct 4.

Division of Dermatology, Department of Medicine, University of Tennessee Health Science Center, Memphis, Tennessee 38163, USA.

In 1996 el Darouti and Abu el Ela described seven Egyptian patients with similar cutaneous lesions and proposed necrolytic acral erythema (NAE) as a distinct entity of the necrolytic erythema family. Since then, NAE has emerged as a cutaneous manifestation of hepatitis C virus infection and taken its place in the literature as a marker for systemic disease. NAE initially presents with burning, pruritic eruptions of circumscribed, erythematous papules with flaccid vesiculation on the acral surfaces universally affecting the dorsum of the feet. Read More

Indian J Dermatol 2011 Mar;56(2):249-50

Department of Dermatology, Ramakrishna Mission Seva Pratisthan, 99, Sarat Bose Road, Kolkata 700 026, West Bengal, India. E-mail:

N Engl J Med 2011 Apr;364(15):1479-80

Dermatol Online J 2010 Nov 15;16(11):15. Epub 2010 Nov 15.

Department of Dermatology, New York University, New York, NY, USA.

Necrolytic acral erythema (NAE) is a recently recognized dermatosis almost exclusively associated with hepatitis C virus (HCV) infection and closely related to a group of necrolytic erythemas and metabolic syndromes. NAE is characterized by pruritic, symmetric, well-demarcated, hyperkeratotic, erythematous-to-violaceous, lichenified plaques with a rim of dusky erythema on the dorsal aspects of the feet and extending to the toes. Based on morphology and histopathologic features, NAE can be difficult to distinguish from certain groups of necrolytic erythemas, which include necrolytic migratory erythema, acrodermatitis enteropathica, biotin deficiency, niacin deficiency, and essential fatty acid deficiencies. Read More

Indian J Dermatol 2010 Jul-Sep;55(3):259-61

Department of Dermatology, KPC Medical College, Kolkata, India.

A patient was referred to us with asymptomatic, erythematous, nonitchy, scaly lesions present bilaterally on the dorsa of his feet and toes since the last 2 months. Both the legs had pitting edema as well. There were hyperkeratosis, focal parakeratosis, acanthosis and scattered spongiosis in the epidermis, and proliferation of capillaries with perivascular infiltration of lymphomononuclear cells in the dermis. Read More

Dig Dis Sci 2010 Oct 26;55(10):2735-43. Epub 2010 May 26.

Department of Medicine, Johns Hopkins Hospital, Baltimore, MD 21287, USA.

Necrolytic acral erythema (NAE) is a member of the necrolytic erythemas, which include necrolytic migratory erythema (NME), acrodermatitis enteropathica, and various dermopathies secondary to nutritional deficiencies. NAE is distinct from the other necrolytic erythemas by virtue of its consistent association with hepatitis C (HCV) together with the acral distribution of its lesions, in particular, dorsal hands and feet. Although its etiology is unknown, NAE has been reported to respond to zinc replacement, suggesting a causal relationship. Read More

J Am Acad Dermatol 2010 Aug 11;63(2):259-65. Epub 2010 May 11.

Department of Dermatology, Faculty of Medicine, Cairo University, Cairo, Egypt.

Background: Leukocytoclastic vasculitis (LCV) and necrolytic acral erythema (NAE) are skin disorders associated with hepatitis C virus (HCV) infection. However, they have not been found to occur simultaneously in the same patient.

Objective: We sought to analyze the role of serum HCV-RNA levels and HCV genotype in the pathogenesis of both LCV and NAE in an attempt to assess whether these two parameters play a role in mutual exclusivity of LCV and NAE in the same patient. Read More

Br J Dermatol 2010 Sep 23;163(3):476-80. Epub 2010 Apr 23.

Dermatology and Venereology Department, Ain Shams University, Cairo, Egypt.

Background: Necrolytic acral erythema (NAE) is considered a cutaneous sign of hepatitis C virus infection. Its exact pathogenesis is still not fully understood, with some reports about decreased serum zinc levels but none about its level in the skin.

Objectives: To assess skin (lesional and perilesional) and serum zinc levels in patients with NAE and compare them with levels in control subjects. Read More

Cutis 2009 Dec;84(6):301-4

Division of Dermatology, Department of Medicine, Cooper University Hospital-University of Medicine and Dentistry of New Jersey/Robert Wood Johnson Medical School, Camden, USA.

Hepatitis C virus (HCV) infection is the most common chronic blood-borne viral infection in the United States. Well-described cutaneous manifestations of HCV infection include polyarteritis nodosa, porphyria cutanea tarda, type II cryoglobulinemia-associated vasculitis, pruritus, erythema nodosum, urticaria and urticarial vasculitis, lichen planus, and erythema multiforme. First described in 1996, necrolytic acral erythema (NAE) is now recognized as a cutaneous acral eruption uniquely associated with HCV infection. Read More

Int J Dermatol 2009 Oct;48(10):1096-9

Department of Dermatology, Krishna Institute of Medical Sciences, Karad, Maharashtra, India.

Background: Necrolytic acral erythema (NAE) is a distinct skin entity and is strongly associated with chronic hepatitis C virus (HCV) infection. It is distinguished by its acral location, typical clinical and histopathologic features, and positive serum antibodies against HCV. Most cases have been treated with variable success using oral zinc, amino acids, and interferon with or without ribavirin therapy. Read More

Cutis 2009 Jun;83(6):309-14

New Jersey Medical School, Newark, USA.

Necrolytic acral erythema (NAE) has been described as an early cutaneous marker for hepatitis C virus (HCV) infection. It most commonly presents as a well-defined, dusky, erythematous eruption with marked hyperkeratosis and a dark red rim associated with pruritus or burning. Necrolytic acral erythema bears microscopic and clinical resemblance to other necrolytic erythemas, including necrolytic migratory erythema (NME) and several nutrient-deficient syndromes. Read More

J Cutan Pathol 2009 Mar;36(3):355-8

Department of Dermatology, Mackay Memorial Hospital, Taipei, Taiwan.

Necrolytic acral erythema is a newly described entity characterized by sharply demarcated scaly plaques on the dorsum of the hands and feet. More than 30 patients have been reported since 1996, all of whom had anti-hepatitis C virus antibody. A 32-year-old Taiwanese woman had been diagnosed with and treated for systemic lupus erythematosus with lupus nephritis about 10 years earlier. Read More

J Am Acad Dermatol 2009 Mar 6;60(3):504-7. Epub 2008 Nov 6.

Department of Dermatology, University of Alabama at Birmingham, Birmingham, Alabama, USA.

We describe a patient who was referred for management of psoriasis unresponsive to treatment. Given the predominantly acral distribution of the patient's rash and his known diagnosis of hepatitis C, we considered the diagnosis of necrolytic acral erythema (NAE) and empirically began treatment with oral zinc sulfate. At follow-up 3 weeks later, the patient had exceptional improvement in his cutaneous disease, supporting our diagnosis of NAE. Read More

Int J Dermatol 2008 Oct;47(10):1073-5

Department of Dermatology, Niazi Medical Complex Hospital, Club Road, Sargodha, Pakistan.

Necrolytic acral erythema is a relatively recently described psoriasis-like skin eruption seen in people infected with hepatitis C virus. Hepatitis C virus infection is endemic in many parts of the world with a steady increase of incidence in Pakistan. Recognition of this disorder is crucial to an early treatment of the underlying liver disease. Read More

Int J Dermatol 2008 Aug;47(8):872-3

Dermatol Online J 2008 Jun 15;14(6):10. Epub 2008 Jun 15.

Department of Dermatology, Baylor College of Medicine, Houston, Texas, USA.

Int J Dermatol 2008 Jul;47(7):709-11

Department of Dermatology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, 1 World's Fair Drive, Somerset, NJ 08879, USA.

Cutis 2008 Apr;81(4):355-60

Department of Dermatology, San Antonio Uniformed Services Health Education Consortium, Fort Sam Houston, Texas, USA.

Necrolytic acral erythema is a novel member of the necrolytic erythema family found exclusively in patients with hepatitis C virus (HCV) infection. Acrally distributed, dusky, erythematous plaques with vesiculation evolve into hyperkeratotic lesions resembling psoriasis. Given the prevalence of chronic HCV infection, necrolytic acral erythema probably is a commonly encountered entity misdiagnosed as an inflammatory dermatosis. Read More

J Med 1999 ;30(3-4):149-56

Dermatology, New Jersey Medical School, 185 South Orange Avenue, Newark, NJ 07103-2714, USA.

Various metabolic events may lead to dermatologic pathology. Three illustrative examples are glucagonoma syndrome, uremic pruritus, and zinc deficiency. The glucagonoma syndrome, resulting from a glucagon secreting-tumor, is characterized by a distinctive dermatitis, necrolytic migratory erythema. Read More

J Am Acad Dermatol 2006 Nov;55(5 Suppl):S108-10

J Gastroenterol Hepatol 2006 Jul;21(7):1200-6

Department of Dermatology and Venereology, Ain Shams University, Cairo, Egypt.

Background: Necrolytic acral erythema (NAE) is a distinctive skin lesion that was first described in 1996 with only few cases being reported, mostly from Egypt. It is unique in its acral distribution and exclusive association with hepatitis C virus (HCV) infection.

Methods: Twenty-three patients (mean age 41. Read More

Int J Dermatol 2005 Nov;44(11):916-21

Department of Dermatology, Faculty of Medicine, Zagazig University, Zagazig, Egypt.

Background: Hepatitis C is a major health problem in Egypt. Necrolytic acral erythema (NAE) is a recently described necrolytic erythema that has a distinctive acral distribution and a uniform association with hepatitis C. Some authors believe that NAE is a distinct entity and others consider it as a variant of necrolytic migratory erythema (NME). Read More

J Am Acad Dermatol 2005 Aug;53(2):247-51

Department of Dermatology and Venereology, Faculty of Medicine Ain Shams University, Cairo, Egypt.

Background: Hepatitis C virus (HCV) infection is globally epidemic. Several mucocutaneous diseases are well established in association with HCV infection. Few case reports describe the recently recognized HCV-related skin disorder termed necrolytic acral erythema (NAE). Read More

Arch Dermatol 2005 Jan;141(1):85-7

Department of Dermatology and Venereology, Faculty of Medicine, Ain Shams University, Cairo, Egypt.

Background: Recently, necrolytic acral erythema (NAE) has been described as a cutaneous marker for hepatitis C virus (HCV) infection. Only 2 cases have been reported in the United States. Successful remission has been induced only with interferon therapy with or without ribavirin. Read More

Eur J Endocrinol 2004 Nov;151(5):531-7

University Medical Center Groningen, Department of Endocrinology, PO Box 30.001, 9700 RB Groningen, The Netherlands.

The glucagonoma syndrome is a rare disease in which a typical skin disorder, necrolytic migratory erythema, is often one of the first presenting symptoms. Weight loss and diabetes mellitus are two other prevalent characteristics of this syndrome. Necrolytic migratory erythema belongs to the recently recognized family of deficiency dermatoses of which zinc deficiency, necrolytic acral erythema and pellagra are also members. Read More

J Am Acad Dermatol 2004 May;50(5 Suppl):S121-4

Department of Dermatology, University of Pennsylvania School of Medicine, Philadelphia, PA 19104, USA.

Necrolytic acral erythema is a papulosquamous and sometimes vesiculobullous eruption bearing clinical and histologic similarity to other necrolytic erythemas such as necrolytic migratory erythema, pseudoglucagonoma, and nutritional deficiency syndromes. Necrolytic acral erythema is distinguished by its association with hepatitis C infection and its predominantly acral distribution. We describe a pediatric patient with necrolytic acral erythema whose eruption resolved with hyperalimentation and combination interferon and ribavirin therapy, despite the persistence of detectable viral load and continued hepatic and renal insufficiency. Read More

J Ark Med Soc 2004 Apr;100(10):354-5

Department of Dermatology, Faculty of Medicine Ain Shams University, Cairo, Egypt.

Described in 1996, necrolytic acral erythema remains the sole diagnostic cutaneous marker for hepatitis C virus infection. To date only eight cases have been described in literature, a fact that makes full histological description and appreciation of the disease process inadequate. Thirty necrolytic acral erythema cases were biopsied and detailed histological description was performed by three separate dermatopathologists who were blinded as to clinical presentation. Read More

Int J Dermatol 2004 Jan;43(1):12-8

Department of Dermatology, Mayo Clinic, Rochester, Minnesota 55905, USA.

Background: The clinical mucocutaneous manifestations of glucagonoma syndrome are recognized easily when they occur in the classic pattern of acral or periorificial lesions evolving in recurrent crops, with an annular and migratory distribution, in a patient with diabetes mellitus who has had recent weight loss and anemia. Not infrequently, noncharacteristic clinical and histopathologic features are observed and, in these cases, the diagnosis of pancreatic neoplasm may be delayed.

Aim: To review the clinical and histopathologic features of cutaneous manifestations of glucagonoma syndrome. Read More