Track

Clinical Studies

Abstract

Distinguishing cutaneous acute graft-versus-host disease (aGvHD) from cutaneous drug eruption/dermal hypersensitivity reaction (CDE/DHR) during the post-stem cell transplantation (SCT) period poses a challenge due to their overlapping clinical and histopathological features. Antigen-presenting dendritic cells (DCs) and NK cells, along with an imbalance in effector regulatory T-cells (Tregs), have been previously implicated in the pathogenesis of aGvHD.

In this study, we assessed the density of DCs, including Langerhans cells and plasmacytoid DCs (pDCs), helper and cytotoxic T-cells, and NK cells in 54 skin specimens from post-SCT patients with grade II aGvHD (n=20), post-SCT patients with CDE/DHR (n=19), and non-SCT patients with CDE/DHR (n=15). We utilized anti-CD4, anti-CD8, anti-CD56, anti-CD123/anti-TCF4, and anti-FOXP3 antibodies for immunohistochemical analysis to quantify the density of each immune cell type. Additionally, histopathological parameters like dyskeratotic keratinocyte density and absolute eosinophil count were recorded.

We observed significant differences in the density of CD56+ NK cells (p=0.002), FOXP3+ Tregs (p<0.001), and TCF4/CD123+ pDCs (p<0.001) among the three groups. Conversely, there were no significant differences in the density of CD4+ helper T-cells and CD8+ cytotoxic T-cells. Utilizing multivariable logistic regression, a combination of CD56, FOXP3, and TCF4/CD123 immunohistochemical studies demonstrated an area under the curve of 0.9, indicating excellent discrimination. Furthermore, statistically significant differences were found in dyskeratotic keratinocyte density (p=0.014) and absolute eosinophil count (p<0.001) among the three groups.

Our results indicate that employing a combinatorial panel of IHC markers like CD56, FOXP3, and CD123/TCF4 could provide additional support in distinguishing cutaneous aGvHD from CDE/DHR within relevant clinicopathological contexts.