Early Neutrophil Activation in Psoriatic Skin at Relapse Following Dead Sea Climatotherapy

Abstract

Psoriasis, a chronic inflammatory skin disorder characterised by erythematous and scaly plaques, can be both physically and emotionally distressing for patients. Dead Sea climatotherapy (DSC), a treatment modality combining sun exposure, mineral-rich water and mud therapy during 4 weeks at Ein Gedi, Israel, is used for a small group of patients with psoriasis. This study aimed to investigate the cellular composition of psoriatic skin lesions at relapse after complete clearance from DSC. Skin biopsies from baseline, end of treatment and relapse were collected from eight patients with plaque psoriasis who achieved complete clearance from Dead Sea climatotherapy treatment. These biopsies were subjected to immunohistochemistry, RNA sequencing and quantitative polymerase chain reaction analysis (qPCR). Our findings demonstrate that DSC effectively reduces inflammatory markers to levels comparable to baseline non-lesional skin in the short term. The differential expression analysis identified several upregulated differentially expressed genes, including OSM, CXCL8, TREM1, CXCL1, CSF3R, BCL2A1 and CXCL2, in relapsed psoriasis skin compared with baseline lesional skin. These findings were confirmed by qPCR analysis. Pathway enrichment analysis indicated a marked upregulation of neutrophil-associated pathways in relapse skin compared with baseline lesional skin. Immunohistochemical staining for neutrophil markers, such as CD11b, CD15, CD66b, CD207, MPO and NE, showed a non-significant trend towards enhanced neutrophil infiltration and activation at relapse. In conclusion, while DSC provides short-term effectiveness in managing psoriasis, the initial relapse phase is associated with neutrophil activation and migration. Thus, targeting neutrophils early in the psoriasis disease course may disturb the evolution of psoriasis, potentially preventing disease chronicity.