Use of methotrexate in recalcitrant eczema.

Sir,

Treatment options for severe or recalcitrant eczemas are limited. Oral or topical steroids are frequently used. Oral steroids have to be prescribed in doses that often lead to debilitating side effects, and therefore, are not a long-term solution. Methotrexate (MTx), in spite of its very pronounced immunomodulatory and anti-inflammatory properties, has not found an appropriate place in the treatment of eczemas.

We conducted a study on the effect of methotrexate in 15 patients (10 male and 5 female) who had severe and recalcitrant eczemas. Age range was between 30 and 60 years. Out of 15 patients, pompholyx was seen in 6, asteatotic (senile) eczema in 2, nummular eczema in 4, while 3 patients had adult onset atopic eczema. Methotrexate was used either as first-line therapy or as an adjunct with topical and systemic therapy, where doses of systemic steroids were prohibitively high (at which the patients started showing signs of steroid side effects). Baseline hemogram, liver function tests, renal-function tests, chest skiagram were performed before initiating methotrexate therapy. Oral methotrexate was used in a dose of 10–15 mg weekly as a single or divided dose. Duration of treatment was at least 12 weeks. Treatment response was graded as follows:

Excellent: At the end of treatment period, there was complete remission with only occasional need of topical steroids.

Good: Partial remission of eczema with decreased requirement of oral steroids, with occasional flare-up.

Poor: No demonstrable change in status of eczema.

Out of 15 patients, excellent response was seen in 7 patients (2 pompholyx, 2 asteatotic eczema, 2 nummular eczema and 1 atopic eczema), while good response was seen in 3 patients (1 pompholyx, 1 nummular eczema and 1 atopic eczema). Five patients showed poor response. Methotrexate was well-tolerated without any drug limiting side effects or laboratory abnormalities in all the patients during the study period of 12 weeks [Table 1].

Table 1

Response to methotrexate

The efficacy of methotrexate is mainly related to its effect on epidermal cell proliferation. However, in vitro studies demonstrate that methotrexate has more significant effect on lymphoid cell. Methotrexate metabolites, methotrexate polyglutamates, can be detected in skin for up to 2 weeks after a single administration. These metabolites cause release of adenosine from cells. Adenosine then occupies specific adenosine receptor and inhibits lymphocyte proliferation as well as pro-inflammatory cytokines TNF-α, IL-6, IL-8, while increasing production of IL-1 receptor antagonist in monocyte.[1] This effect on inflammatory cytokines may explain its beneficial effect in eczema. We tested this hypothesis in an attempt to look into the potential benefits that methotrexate could offer in recalcitrant or difficult to treat eczema.

There are only a few studies in literature supporting the role of methotrexate in eczema.[23] The study conducted by Conleth et al.[2] showed significant improvement with methotrexate in five patients of recalcitrant palmoplantar pompholyx, who did not respond to conventional therapy or who had debilitating side effects from corticosteroids. The doses of methotrexate used by them were comparable to doses used by us or even higher. Their patients also tolerated methotrexate well.

Our results indicate that methotrexate deserves to be further explored in treatment of difficult to treat eczemas.