Methotrexate versus Acitretin in the Treatment of Chronic Hand Dermatitis

alitretinoin for hand dermatitis in most of Europe and Canada in 2008, and it remains the only licensed systemic treatment for hand dermatitis. In 2012, Diepgen et al investigated the use of alitretinoin to treat CHD under daily “real life” medical practice conditions in Germany. In total, 56.7% of patients achieved a clear or almost clear response, with only small differences in patients with different morphological forms: hyperkeratotic-rhagidiform (59.2%), fingertip (52.2%), and vesicular (47.9%).⁷ Recently, Fowler et al reported that 40% of patients treated with alitretinoin 30 mgs daily achieved a clear or almost clear response after 24 weeks of treatment.⁸ Alitretinoin is not currently licensed for use in the United States.

In view of these results, we treated some of our patients with acitretin, a retinoid available in the United States. Acitretin inhibits the expression of pro-inflammatory cytokines interleukin-6 (IL-6), migration inhibitory factor-related protein-8 (MRP-8), and interferon-gamma (markers of hyperproliferation and abnormal keratinocyte differentiation). It acts as an anti-inflammatory and antiproliferative, resulting in keratinocyte differentiation and normalization of the epithelium.^9-11 This combination of anti-inflammatory and antiproliferative effects explains one possible mechanism for the success of acitretin in treatment of the hyperkeratotic variant.

For all CHD patients treated with acitretin (with or without methotrexate), we noted statistically significant responses compared to methotrexate (without acitretin) at 6 months (P = 0.0353). Although the sample was small, a better response to acitretin was also noted at 12 months. (Table 2) The doses of acitretin and methotrexate varied among patients based on safety, tolerability, and efficacy considerations. The response can be relatively slow, with 3 to 6 months required to achieve a maximal response.¹² The average patient dose was 27.46 mg/d for acitretin and 12.79 mg/week for methotrexate.

Adverse effects are summarized in Table 2. These adverse effects are comparable to those described by Dunn et al. in a literature review of acitretin in 2011.13 Although a majority of patients experienced abnormal laboratory values, none were severe enough to require discontinuation. Hypertriglyceridemia was successfully managed through dietary modifications or dose reductions.

Acitretin should not be used in women of childbearing potential unless other treatment options are exhausted and the benefits outweigh the risks. When its use is merited, contraception must be used and pregnancy must be avoided for three years due to the potential conversion of acitretin to etretinate.¹⁴ In this study, there were no female patients of childbearing potential treated with acitretin.

We believe that acitretin merits further clinical evaluation regarding its efficacy in CHD patients, and it should potentially be the drug of choice for patients with CHD.

Study limitations include UNC serving as a referral center for many of these patients with CHD, small sample size, selection bias in evaluating patients for different treatments, and selection bias due to treatment potential in females with child-bearing potential.

The authors have no conflict of interest to declare.