Necrolytic Acral Erythema in Seronegative Hepatitis C Patient with Vitamin B12 Deficiency.

Sir,

Necrolytic acral erythema (NAE) is an important cutaneous diagnostic marker for hepatitis C infection (HCV).[1] It has also been described with low serum zinc levels.[2] Cases of NAE in seronegative Hepatitis C with normal zinc levels and Vitamin B12 deficiency are rare in the literature, which led to the present report.

Our patient, a 40-year-old female presented with complaints of dark-colored itchy lesions over both the feet of 08 months duration with the absence of similar scaly lesions over hands or elsewhere on the body. Dermatological examination revealed sharply defined, bilaterally symmetrical, nontender, hyperpigmented scaly plaques with distinct marginal erythema over the dorsal aspect of both feet extending to the distal end of toes [Figure 1]. Differential diagnosis of chronic plaque psoriasis, allergic contact dermatitis to slippers, and tinea pedis were considered; however, Grattage test and Auspitz sign were negative, patch test to standard Indian Series Battery was negative, and KOH mount for fungal hyphae was negative for fungal elements. On investigations, her Vitamin B12 levels were found to be 130 pg/ml (normal 187–883 pg/ml) with normal zinc levels. The patient was seronegative for HCV infection. All other hematological and biological parameters were within normal limits. Histopathological findings were consistent with NAE: hyperkeratosis, focal papillomatosis, variable acanthosis, spongiosis, and scattered individual keratinocyte necrosis. Pigment incontinence along with mild lymphocytic infiltrate was present. [Figure 2]. She was started on Vitamin B12 supplementation 1500 mcg orally for 06 months with an initial application of Beclomethasone (0.1%) + Salicylic Acid (3%) for symptomatic relief from itching for 02 weeks. The patient showed good response to therapy with reduction in erythema, scaling, and induration in that order over the next 5 months [Figure 3]. She was administered an additional 1 month of vitamin B12 and then discontinued. She continues to be asymptomatic 6 months later.

Figure 1

Sharply defined, bilaterally symmetrical, hyperpigmented scaly plaques with distinct marginal erythema over the dorsal aspect of both feet extending to the distal end of toes

Figure 2

Hyperkeratosis, focal papillomatosis, and variable acanthosis and spongiosis present. Pigment incontinence along with mild lymphocytic infiltrate and individual keratinocyte necrosis was also seen, consistent with necrolytic acral erythema H and E 100×

Figure 3

Good response to therapy with reduction in erythema, scaling and induration

NAE belongs to the group of necrolytic erythemas with unknown pathogenesis. However, it is thought to be related to zinc dysregulation, which can occur due to HCV-induced metabolic alteration.[3] This condition is associated with decreased zinc levels in both the serum and the skin. Other causes such as metabolic alterations including hypoalbuminemia, hypoaminoacidemia, hyperglucagonemia, liver dysfunction, and diabetes have been proposed.[4] NAE is classically located at the acral sites, characterized by hyperpigmented plaques with clear border of erythema. Treatment in the literature ranges from oral zinc supplementation to antiviral therapy for HCV (Interferon-alpha with or without ribavirin).[5] Limited number of cases have been described with hepatitis C seronegative status and normal zinc levels [Table 1].[345678] We did not come across any case of association of NAE with Vit B12 deficiency in the literature which makes our case interesting.

Table 1

Review of seronegative necrolytic acral erythema

Report	Year	Age and sex	Clinical features	Serum zinc levels
Wu et al.[6]	2009	32/M	Pruritic scaly plaques over dorsum of both hands and feet	Low-453 mcg/dl
Nikam[7] (02 cases)	2009	38/M 25/F	Both cases have itchy, papulo-squamous lesions over dorsa of feet and hands	Case 1-normal Case 2-not done
Panda and Lahiri[8]	2010	68/M	Nonpruritic erythematous plaques over dorsum of bilateral palms and soles	Borderline-60 mcg/dl
Pandit et al.[5] (02 cases)	2016	24/M 40/M	Case 1: Well defined hyperpigmented plaques with vesicles and bullae Case 2: Well defined hyperpigmented plaques	Case 1 and 2-low
Das et al.[4]	2016	30/F	Hyperpigmented scaly plaques over dorsum of hand and feet	Not done
Srisuwanwattana and Vachiramon[3]	2017	64/F	Brown to hyperpigmented plaques over lateral malleoli	Normal

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Conflicts of interest

There are no conflicts of interest.