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CORRESPONDENCE Table of Contents  
Ahead of print publication
Zinc-responsive seronegative necrolytic acral erythema: A case report and literature review

1 Department of Dermatology, Taipei Veterans General Hospital; Faculty of Medicine, School of Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan
2 Department of Dermatology, Taipei Veterans General Hospital; Faculty of Medicine, School of Medicine; Department of Dermatology, National Yang Ming Chiao Tung University, Taipei, Taiwan
3 Department of Dermatology, Taipei Veterans General Hospital; Faculty of Medicine, School of Medicine; Department of Dermatology; Institute of Brain Science, National Yang Ming Chiao Tung University, Taipei, Taiwan

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Date of Submission25-May-2022
Date of Decision31-Jul-2022
Date of Acceptance01-Aug-2022
Date of Web Publication20-Oct-2022

How to cite this URL:
Wei YH, Ma SH, Chang YT, Li CY. Zinc-responsive seronegative necrolytic acral erythema: A case report and literature review. Dermatol Sin [Epub ahead of print] [cited 2022 Nov 28]. Available from: https://www.dermsinica.org/preprintarticle.asp?id=359342

A 17-year-old woman has a history of iron deficiency anemia. She suffered from itchy skin eruption over bilateral lower legs for 4 years without other systemic symptoms. On physical examination, multiple well-demarcated painful and pruritic, arcuate-shaped, erythematous plaques with a distinctive inflamed and erosive rim at the periphery, over her bilateral dorsal feet and ankles were observed [Figure 1]a and [Figure 1]b. Skin scraping with potassium hydroxide staining produced a negative result. Topical steroids and vitamin D were used, but the symptoms were only relieved partially. Thus, two incisional biopsies were performed, with one on the long-standing scaly plaque and another on the newly formed lesions at the periphery.
Figure 1: (a) Clinical image of the erythematous scaly plaque over the left foot, (b) Clinical image of the erythematous scaly plaque over the left ankle. Note the distinct erythematous, erosive border

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Histopathology examination of the scaly plaque showed parakeratosis and psoriasiform hyperplasia [Figure 2]a. Another biopsy at the periphery revealed intraepidermal cleft and focal epidermal pallor and necrosis [Figure 2]b. Several disease entities may show similar pathological features, including necrolytic acral erythema (NAE), necrolytic migratory erythema, and pellagra. The patient denied diarrhea, dysgeusia, weakness, poor wound healing, or other discomforts other than skin lesions. Physical examination revealed no neurological signs, and laboratory data showed a normal endocrine profile, albumin level and fasting glucose level, negative hepatitis C infection, and relative low zinc level (51 μg/dL; normal range: 60–120 μg/dL). Since her skin lesions were confined to her bilateral feet without periorificial involvement, seronegative NAE was a favored diagnosis. Zinc supplement (150 mg/day; 1.27/mg/kg/day) was initiated, and her symptoms showed dramatic improvement thereafter [Figure 3].
Figure 2: (a) Pathology of the erythematous plaque. Hematoxylin and eosin staining demonstrates parakeratosis, loss of granular layer, and psoriasiform hyperplasia (H and E, ×100), (b) Pathology of the erosive border. Hematoxylin and eosin staining reveals intraepidermal cleft and focal epidermal pallor and necrosis (H and E, ×100)

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Figure 3: Clinical image of the patient 2 months after zinc supplement. Only residual postinflammatory hyperpigmentation remained

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  Discussion Top

NAE is a rare disease characterized by well-demarcated, erythematous to violaceous, scaly plaques over the acral area, especially the dorsum of the hands and feet. Besides, in the acute stage, erythema may be prominent at the border with flaccid blisters, erosion, and crust formation.[1] Given the variety of clinical manifestations, NAE is usually difficult to diagnose.

Most cases of NAE have a history of chronic hepatitis C infection, but the exact pathophysiology is still poorly understood. Zinc may play a part in the pathophysiology, as some patients had concomitant zinc deficiency and responded well after taking zinc supplements.[2] Moneib et al. further found that zinc levels, in both serum and skin, were significantly lower in patients with NAE.[3] These studies support that a low acral epidermal zinc level is, to some extent, involved in the development of NAE.

Although rare, NAE may also develop in patients without hepatitis C virus infection. The etiologies of seronegative NAE are diverse, including drugs, immune dysregulation, and zinc deficiency; however, the etiology remained unknown in some cases.[4],[5],[6] In our case, her NAE could be partially explained by a relatively low zinc level, and the response after the zinc supplement was dramatic. The pathology of NAE is also quite variable. In the acute stage, parakeratosis, scattered dyskeratotic keratinocytes and epidermal upper pallor and necrosis are the main features.[7] However, in fully-developed lesions, biopsy may reveal psoriasiform hyperplasia with parakeratosis, which is relatively nonspecific. Thus, biopsy over acute lesions is warranted for an accurate diagnosis.

In summary, in patients with focal psoriasiform eruption over the acral area, NAE should be listed as a differential diagnosis. Skin biopsy at acute-staged lesions might facilitate the diagnosis. Aside from hepatitis C infection, zinc levels should also be checked, and adequate zinc supplementation may be considered as a treatment option.

Declaration of patient consent

The authors certify that they have obtained all appropriate patient consent forms. In the form, the patient has given her consent for her images and other clinical information to be reported in the journal. The patient understands that name and initials will not be published and due efforts will be made to conceal identity, but anonymity cannot be guaranteed.

Financial support and sponsorship

This study was funded by the Ministry of Science and Technology, R.O.C., under Grant “MOST 107-2314-B-075-032-MY3-2” and “MOST 110-2314-B-075-068.”

Conflicts of interest

Prof. Yun-Ting Chang, an editorial board member at Dermatologica Sinica, had no role in the peer review process of or decision to publish this article. The other authors declared no conflicts of interest in writing this paper.

  References Top

Tabibian JH, Gerstenblith MR, Tedford RJ, Junkins-Hopkins JM, Abuav R. Necrolytic acral erythema as a cutaneous marker of hepatitis C: Report of two cases and review. Dig Dis Sci 2010;55:2735-43.  Back to cited text no. 1
Najarian DJ, Lefkowitz I, Balfour E, Pappert AS, Rao BK. Zinc deficiency associated with necrolytic acral erythema. J Am Acad Dermatol 2006;55:S108-10.  Back to cited text no. 2
Moneib HA, Salem SA, Darwish MM. Evaluation of zinc level in skin of patients with necrolytic acral erythema. Br J Dermatol 2010;163:476-80.  Back to cited text no. 3
Pathania YS, Budania A. Rivaroxaban induced necrolytic acral erythema. Postgrad Med J 2019;95:563.  Back to cited text no. 4
Das A, Kumar P, Gharami RC. Necrolytic acral erythema in the absence of hepatitis C virus infection. Indian J Dermatol 2016;61:96-9.  Back to cited text no. 5
[PUBMED]  [Full text]  
Wu YH, Tu ME, Lee CS, Lin YC. Necrolytic acral erythema without hepatitis C infection. J Cutan Pathol 2009;36:355-8.  Back to cited text no. 6
Pandit VS, Inamadar AC, Palit A. Seronegative necrolytic acral erythema: A report of two cases and literature review. Indian Dermatol Online J 2016;7:304-7.  Back to cited text no. 7
[PUBMED]  [Full text]  

Correspondence Address:
Cheng-Yuan Li,
Department of Dermatology, Taipei Veterans General Hospital, No. 201, Sec. 2, Shipai Road, Beitou, Taipei 11217
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1027-8117.359342


  [Figure 1], [Figure 2], [Figure 3]


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