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Methotrexate treatment for refractory adult atopic dermatitis leads to changes in the cutaneous expression of IL-31 and IL-31RA, according to a recent study.

Atopic dermatitis (AD) is a chronic skin disease with a complex pathophysiology. AD treatment requires inflammation reduction and skin barrier repair. Therefore, methotrexate (MTX) may serve as a treatment for patients with AD refractory to traditional therapy. 

A study in Anais Brasileiros de Dermatologia evaluated the effect of MTX on cutaneous cytokine and chemokine expression in AD.

Study Population

The study comprised 12 adults (6 males, 6 females) with moderate to severe AD. The patients received MTX treatment for a total of 24 weeks.

Methotrexate Treatment Reduced Epidermal Thickness

The mean epidermal thickness in the lesional skin of AD patients before treatment was 127.6 ±194.3 µm. After MTX treatment, the mean epidermal thickness was 100.3 ±80.7 µm. The mean epidermal thickness was significantly less in the post-treatment lesional skin vs. pre-treatment with MTX (mean difference: 31.3 µm, 95% confidence interval: 15.0–92.7; p = 0.021).

Methotrexate Treatment Increased Expression of IL-31RA 

Increased expression of the interleukin-31 alpha-receptor subunit (IL-31RA) was observed in the epidermal samples from AD patients after MTX treatment (p = 0.016) as compared to before treatment. There was no significant difference in the superficial dermis sample (p = 0.151) before and after treatment. There were no significant changes in the cutaneous expression of other markers, i.e., oncostatin M receptor (OSMR), thymic stromal lymphopoietin (TSLP), and antigen Kiel (Ki-67).

Methotrexate Treatment Decreased IL-31 Gene Expression

There was a decrease in the IL-31 gene expression (p = 0.019) in the lesional skin of AD patients after 24 weeks of MTX therapy. There were no significant changes in the cutaneous expression of the other evaluated markers, i.e., IL-4, IL-6, IL-10, IL-31RA, tumor necrosis factor-alpha (TNF-α), interferon gamma (IFN-γ), thymus and activation-regulated chemokine (TARC), and C-C motif chemokine 22 (CCL-22). The increased epidermal expression of IL-31RA, as shown by immunohistochemistry, suggests a compensatory mechanism, given the reduction in IL-31 gene expression.

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In conclusion, patients with moderate to severe AD treated with MTX showed reduced epidermal hyperplasia and altered expression of inflammatory cytokines and receptors related to pruritus, including IL-31 and IL-31RA. Large-scale studies with longer follow-up durations are recommended to further track changes in the cutaneous expression of inflammatory markers in AD patients receiving MTX treatment.


Samorano, L. P., Gomes, K. C., Pereira, N. L., Takaoka, R., Valente, N. Y. S., Sotto, M. N., Da Silva, L. F. F., Sato, M. N., & Aoki, V. (2023). Methotrexate for refractory adult atopic dermatitis leads to alterations in cutaneous IL-31 and IL-31RA expression. Anais Brasileiros De Dermatologia. https://doi.org/10.1016/j.abd.2023.01.002