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CORRESPONDENCE
Year : 2016  |  Volume : 61  |  Issue : 1  |  Page : 96-99
Necrolytic acral erythema in the absence of hepatitis C virus infection


1 Department of Dermatology, Medical College and Hospital, Kolkata, India
2 Department of Dermatology, Katihar Medical College, Bihar, India

Date of Web Publication15-Jan-2016

Correspondence Address:
Anupam Das
Department of Dermatology, Medical College and Hospital, Kolkata
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/0019-5154.174047

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How to cite this article:
Das A, Kumar P, Gharami RC. Necrolytic acral erythema in the absence of hepatitis C virus infection. Indian J Dermatol 2016;61:96-9

How to cite this URL:
Das A, Kumar P, Gharami RC. Necrolytic acral erythema in the absence of hepatitis C virus infection. Indian J Dermatol [serial online] 2016 [cited 2019 Jul 18];61:96-9. Available from: http://www.e-ijd.org/text.asp?2016/61/1/96/174047


Sir,

Necrolytic acral erythema (NAE) is thought to be a reliable diagnostic marker of infection by hepatitis C virus (HCV). We hereby describe a case of a 30-year-old lady who was referred to us with treatment refractory bilaterally symmetrical plaques on the dorsum of hands and feet. Histology revealed hyperkeratosis, parakeratosis, acanthosis and perivascular mononuclear cell infiltrate. On the basis of clinical and histological features, a diagnosis of NAE was done for our patient. She was found to be seronegative for HCV infection, but showed dramatic response to oral zinc therapy. Very few cases of seronegative NAE have been reported in English literature, which prompted the present report.

A 30-year-old housewife presented with erythematous, pruritic, scaly lesions on the hands and feet, which were present over the preceding 4 years. To start with, there were a few fluid-filled as well as pus-filled lesions over the dorsum of hands. Gradually these were replaced by tender red-colored raised skin lesions. In due course of time, similar lesions appeared on the feet as well. There was no history of trauma. Family history was unremarkable. She had been treated for psoriasis and allergic contact dermatitis for many months, before being referred to us. She had been prescribed steroids (oral, topical and intralesional) earlier, but there was no response. Past medical and surgical history was non-contributory. General examination revealed a well-built lady with normal vital parameters.

Cutaneous examination showed bilaterally symmetrical well-demarcated, scaly plaques on the dorsum of hands and feet. The lesions were surrounded by erythematous margins [Figure 1]. The lesions of feet showed a sharp cut-off at the lateral and medial borders, without any extension to the soles. Besides, there was evidence of lichenification over the plaques as well. There was no edema or ulceration over the acral parts. The hairs, nails and mucosae were absolutely normal. The clinical differentials were psoriasis, eczema, allergic contact dermatitis and tinea. Routine laboratory investigations including serum biochemistry panel, thyroid function tests, renal and hepatic profilewere done. The ESR was 36 mm/hr and CRP was 23 mg/L. Otherwise, the investigation profile was normal. Hepatitis B virus (HBV) and HCV serology were negative. Routine urine and stool examination was non-contributory. Potassium hydroxide mount of scrapings obtained from the lesions did not show any fungal hyphae. Result of patch testing with the Indian Standard Battery was negative. Histological examination of a punch biopsy specimen showed hyperkeratosis, focal parakeratosis, acanthosis and spongiosis. Dermis showed proliferation of capillaries with perivascular mononuclear cell infiltrate [Figure 2] and [Figure 3]. Based on history, clinical examination and histopathology, a diagnosis of NAE was made. Other possibilities of necrolytic erythema were ruled out on clinical grounds. The patient was put on zinc sulfate tablet (100 mg twice daily) and antihistamines. After 2 weeks, the response was dramatic [Figure 4]. The erythema and scaling had diminished substantially. At the end of 4 weeks, the lesions had completely healed with residual hyperkeratosis of both feet, whereas the lesions over the hands healed without any scarring [Figure 5] and [Figure 6].
Figure 1: Clinical photograph showing bilaterally symmetrical well-demarcated, scaly plaques on the dorsum of hands and feet. Note the surrounding erythematous margins. (1st visit)

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Figure 2: Photmicrograph showing hyperkeratosis, focal parakeratosis, acanthosis and spongiosis. Dermis showing proliferation of capillaries with perivascular mononuclear cell infiltrate. (H and E, 10X)

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Figure 3: Photmicrograph showing focal parakeratosis and spongiotic dermatitis. (H and E, 40X)

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Figure 4: Clinical photograph showing dramatic response to zinc at the end of 2 weeks, the response was dramatic. Note the diminution in the erythema and scaling

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Figure 5: Clinical photograph showing complete resolution of skin lesions without any scarring at the end of 4 weeks

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Figure 6: Clinical photograph showing resolution of lesions of feet with residual hyperkeratosis and scarring at the end of 4 weeks

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NAE is a dermatosis, characterized by its hallmark acral location and strong association with HCV infection. [1],[2],[3] Most of the reports have come from Egypt where hepatitis C is a major health problem. In a report by El-Ghandour et al., 23 patients were described. 91.3% of the patients were adults. Besides, 78.3% of the skin lesions were of chronic nature; and almost all the cases were characterized by involvement of the dorsa of the toes and/or feet. [4] The age of onset varies from 35 to 55 years and there is no gender predilection.

NAE strongly suggests underlying HCV infection. However, NAE has not been reported from United States where HCV infection is the most common chronic blood-borne viral infection. Adding to this, Japan has a very high prevalence rate of HCV infection, but reports of NAE are rare. Many cases of NAE have also occurred in patients without hepatitis C. [5],[6],[7],[8] Recently, a case of NAE following hepatitis B vaccination was reported and this was the first of its kind. [9] Upcoming reports of NAE in the absence of an underlying HCV infection warrant more work in this field. Adding to this, it is being proposed that zinc dysregulation per se could be a mandate for the development of NAE.

The pathogenesis is not clear yet, but a relationship with metabolic alterations including hypoalbuminemia, hypoaminoacidemia, hypozincemia, hyperglucagonemia, liver dysfunction, and diabetes has been proposed. Substantial and sustained remission of cutaneous lesions occurs in patients responsive to antiviral therapy. In the setting of HCV infection, a direct correlation exists between severity of cutaneous disease and degree of hepatic damage. Hepatitis C viral load and genotype could also play a pivotal role in the etiopathogenesis of NAE. [10],[11]

Clinically, it is characterized by itchy, bilaterally symmetrical, erythematous-to-violaceous plaques on the dorsum of lower leg. It has to be differentiated from psoriasis and acrokeratosis neoplastica of Bazex. Histologically, early stage of NAE resembles nummular dermatitis, manifested as spongiosis and perivascular dermatitis. However, a full-blown disease is characterized by psoriasiform hyperplasia. [12] NAE should be differentiated from acrodermatitis enteropathica, biotin deficiency, niacin deficiency, necrolytic migratory erythema, and essential fatty acid deficiencies. Diagnosis of the condition is crucial because patients mostly present to the clinicians, in the absence of an underlying HCV infection.

Cases with HBV and HCV seropositivity are best treated using ribavirin and interferon alfa. However, resolution of NAE can also be achieved by oral zinc therapy which may be an alternative but useful therapy. Zinc is anti-apoptotic as well as a cofactor in DNA replication, transcription, translation and Vitamin A metabolism in liver. Zinc deficiency causes a reduction in serum transport proteins like retinol-binding protein and prealbumin which impair delivery of nutrients such as vitamin A to tissues. Vitamin A is indispensable for epidermal proliferation and differentiation. This mechanism may contribute to the development of lesions of NAE. [11],[13]

In this report, our patient was found to be seronegative for anti-HCV antibodies. She was successfully treated with oral zinc. It is a well-known fact that NAE reflects underlying HCV infection but it is likely that NAE could be an autonomous disease and the presence of HCV infection is not mandatory for the disease. In some parts of the world including India, NAE could be a frequently misdiagnosed entity. Clinicians need to be more aware regarding the diagnosis and management of NAE. Our case adds to the literature of very few cases which are not associated with underlying HCV infection [Table 1]. To the best of our knowledge, less than five cases of seronegative necrolytic acral erythema have been reported from India, thus inciting us to report the case.
Table 1: The literature of zinc-responsive, HCV-seronegative cases of necrolytic acral erythema


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   References Top

1.
el Darouti M, Abu el Ela M. Necrolytic acral erythema: A cutaneous marker of viral hepatitis C. Int J Dermatol 1996;35:252-6.  Back to cited text no. 1
    
2.
Abdallah MA, Ghozzi MY, Monib HA, Hafez AM, Hiatt KM, Smoller BR, et al. Necrolytic acral erythema: A cutaneous sign of hepatitis C virus infection. J Am Acad Dermatol 2005;53:247-51.  Back to cited text no. 2
    
3.
Khanna VJ, Shieh S, Benjamin J, Somach S, Zaim MT, Dorner W Jr, et al. Necrolytic acral erythema associated with hepatitis C: Effective treatment with interferon alfa and zinc. Arch Dermatol 2000;136:755-7.  Back to cited text no. 3
    
4.
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 2006;21:1200-6.  Back to cited text no. 4
    
5.
Liu A, Erickson CP, Cockerell CJ, Hsu S. Necrolytic acral erythema: A case not associated with hepatitis C infection. Dermatol Online J 2008;14:10.  Back to cited text no. 5
    
6.
Nikam BP. Necrolytic acral erythema seronegative for hepatitis C virus- two cases from India treated with oral zinc. Int J Dermatol 2009;48:1096-9.  Back to cited text no. 6
    
7.
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. 7
    
8.
Panda S, Lahiri K. Seronegative necrolytic acral erythema: A distinct clinical subset?. Indian J Dermatol 2010;55:259-61.  Back to cited text no. 8
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9.
Pernet C, Guillot B, Araka O, Dereure O, Bessis D. Necrolytic acral erythema following hepatitis B vaccination. Br J Dermatol 2014;171:1255-6.  Back to cited text no. 9
    
10.
El-Darouti MA, Mashaly HM, El-Nabarawy E, Eissa AM, Abdel-Halim MR, Fawzi MM, et al. Leukocytoclastic vasculitis and necrolytic acral erythema in patients with hepatitis C infection: Do viral load and viral genotype play a role?. J Am Acad Dermatol 2010;63:259-65.  Back to cited text no. 10
    
11.
Fielder LM, Harvey VM, Kishor SI. Necrolytic acral erythema: Case Report and Review of the Literature. Cutis 2008;81:356-60.  Back to cited text no. 11
    
12.
Abdallah MA, Ghozzi MY, Monib HA, Hafez AM, Hiatt KM, Smoller BR, et al. Histological study of necrolytic acral erythema. J Ark Med Soc 2004;100:354-5.  Back to cited text no. 12
    
13.
Patel U, Loyd A, Patel R, Meehan S, Kundu R. Necrolytic acral erythema. Dermatol Online J 2010;16:15.  Back to cited text no. 13
    


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