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.
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.
Source:
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
