Photo Credit: Dermatology11

The following is a summary of “Single-cell RNA sequencing of chronic idiopathic erythroderma defines disease-specific markers,” published in the December 2024 issue of Allergy and Immunology by Chennareddy et al. 

Chronic erythroderma can result from various diseases, with 30% of cases remaining idiopathic. Treatment options for these cases are often limited. 

Researchers conducted a retrospective study to establish a molecular disease map of chronic idiopathic erythroderma (CIE). 

They performed single-cell RNA sequencing and T-cell receptor sequencing on blood and skin samples from 5 patients with CIE. Results were compared with 8 erythrodermic cutaneous T-cell lymphoma (eCTCL) cases, 15 moderate-to-severe atopic dermatitis (AD) cases, 10 psoriasis cases, and 20 healthy control (HC) individuals. 

The results showed strong expansion of CD4⁺ malignant clones with a CCR7⁺SELL⁺ central memory phenotype in erythrodermic CTCL. In contrast, CIE showed low-level but consistent expansion of CD8A⁺KLRK1⁺ T-cell clones in blood and skin. KLRK1 was expressed by CCR10⁺FUT7⁺ skin-homing CIE blood T-cells with increased proliferation, absent in all other conditions. Both CIE and CTCL lacked type 2 or type 17 immune skewing but exhibited upregulation of MHC II genes (HLA-DRB1, HLA-DRA, CD74) in keratinocytes and fibroblasts, likely IFNG-dependent. CIE showed the strongest upregulation of type 1 immune mediators in expanded CD8A⁺ clones and tissue microenvironment. 

Investigators identified specific pathogenic signatures in CIE that differentiated it from other forms of erythroderma. These findings enhanced the understanding of CIE and may guide the discovery of future treatment targets. 

Source: jacionline.org/article/S0091-6749(24)02356-X/fulltext