Might Necrotic Keratinocytes Contribute to the Diagnosis and Pathogenesis of Psoriasis?

Introduction: Psoriasis is a chronic inflammatory skin disease that can pose challenges for histopathological diagnosis. Recent research has emphasized the importance of necrotic keratinocytes, meaning keratinocytes undergoing programmed cell death, for diagnosing psoriasis. It has also become increasingly evident that programmed cell death pathways play a significant role in psoriasis's pathogenesis, development, and progression, including via a recently identified programmed cell death mechanism called "PANoptosis."

Objectives: In our study, we aimed to investigate the significance of necrotic keratinocytes in both the diagnosis and pathogenesis of psoriasis.

Methods: We analyzed the number of necrotic keratinocytes in 135 samples of psoriasis, 57 samples of psoriasiform spongiotic dermatitis, and 71 samples of normal skin. We additionally assessed the distribution of necrotic keratinocytes in the upper, middle, and lower thirds of the epidermis.

Results: Our findings revealed a significant difference in the total number of necrotic keratinocytes and their distribution within epidermal regions between patients with psoriasis and both the psoriasiform spongiotic dermatitis and control groups (p < .001). In particular, necrotic keratinocytes were predominantly found in the upper epidermis (77.5%) in patients with psoriasis. We also observed a strong correlation between Psoriasis Area and Severity Index scores and the total count of necrotic keratinocytes in patients with psoriasis (r = .72).

Conclusions: Our results highlight the role of necrotic keratinocytes, resulting from programmed cell death, as important marker cells in both the diagnosis and pathogenesis of psoriasis.