Diagnosing necrolytic acral erythema: does anything go?

Sir,

I read with great interest the informative article “Seronegative necrolytic acral erythema: A distinct clinical subset?” by Panda and Lahiri, published in your esteemed Journal.[1] I have a few questions regarding the validity of the diagnosis of the case presented by Panda and Lahiri.

Most of the cases of necrolytic acral erythema (NAE) are associated with hepatitis C virus infection, and only a few cases have so far been reported without associated hepatitis C infection. The authors considered the case reported by them as an addition to the list of these few cases.

On the basis of the clinical features of the case, the authors have considered the differential diagnoses of psoriasis, eczema, Tinea pedis et unguium, and NAE. The authors have mentioned that involvement of plantar surface and nails in their case was an atypical feature for NAE. Histopathology was not conclusive. A punch biopsy specimen showed hyperkeratosis, focal parakeratosis, acanthosis and scattered spongiosis in the epidermis, and proliferation of capillaries with perivascular infiltration by lymphomononuclear cells in the dermis. The authors have mentioned that absence of reticular degeneration of superficial keratinocytes with dyskeratosis and vacuolization of basal keratinocytes on microscopy are atypical histological features for NAE.[1]

The authors′ diagnosis rests on several purportedly characteristic features including the classic morphology – well-defined, erythematous eruption with marked scaling and a dark red skin, acral distribution, corroborative laboratory findings (low serum albumin and low-normal zinc levels) and a dramatic response to oral zinc supplementation in spite of serum zinc level being within normal limits. But the distribution was not “classic” and the morphology was not distinctive enough to differentiate it from psoriasis, eczema, and tinea. The histopathology did not rule out chronic eczema. Low serum albumin and low-normal zinc levels are common enough to be found as nonsignificant incidental findings. The ostensible “dramatic response to oral zinc supplementation” may be due simply to clobetasol propionate cream applied twice daily for 3 weeks; any case of eczema might have responded with this regimen.

The authors have cited three reports of cases of NAE without associated hepatitis C infection as references. In the case presented in the first article cited, the clinical features were typical of NAE, wherein “…well-demarcated erythematous plaques with scattered bullae were present on the dorsal toes bilaterally”, and histopathology was quite unique, i.e. “… orthokeratosis overlying an epidermis with prominent pallor in the upper third of the epidermis and extensive ballooning of superficial keratinocytes”.[2]

The case presented in the second article cited by Panda and Lahiri has the following clinical features: “… several well-demarcated keratotic plaques with erythematous borders on her feet, with sparing of the soles”. Histopathology showed “diffuse parakeratosis with a neutrophil infiltrate, hypogranulosis, pale upper keratinocytes, scattered and grouped dyskeratotic cells, psoriasiform hyperplasia and a mild lymphocytic infiltrate in the upper dermis. The diagnosis was made after three biopsies”.[3] The biopsies were repeated, and the final diagnosis was not made before getting dyskeratotic cells.

The third article describing cases of NAE without associated hepatitis C infection, cited by Panda and Lahiri, was by Nikam.[4] Here too, one case was clinically and histologically quite typical NAE, and the other case, although not typical NAE, responded to oral zinc alone. The findings of all the cases except the last one cited by the authors are quite clear-cut as compared to the nonspecific clinical and histopathologic findings of the authors′ case.

Panda and Lahiri have cited another article with a very interesting title: “Lack of classic histology should not prevent diagnosis of necrolytic acral erythema”, and refer to this article as their defense for labeling their case as NAE.[5] The authors have cited an article by Bentley et al. which deals with a case that had really atypical clinical and histopathological features but hepatitis C antibody was positive. For a disease in which most cases have been reported in association with hepatitis C, the presence of hepatitis C makes it justifiable to look at the seemingly atypical features in a different light as compared to the same atypical features in a case not associated with hepatitis C. So, it seems Panda and Lahiri have chosen the wrong yardstick to judge the value of the atypical findings their case.

In conclusion, it may be said that the case reported by Panda and Lahiri is compatible with the diagnosis of NAE, but enough evidence has not been produced by the authors to label it with that diagnosis.