Background Psoriasis is considered as an immune‐mediated disorder with significant epidermal hyperplasia and inflammation. Cysteine‐rich angiogenic inducer 61 (CYR61), known as CCN family member 1 (CCN1), plays an important role in cell proliferation and neovascularization which may trigger psoriasis development. Aims This study aimed to assess the immunostaining of CYR61 in psoriatic skin (lesional and perilesional) compared to control skin. Patients/Methods This is a case‐control study. The Psoriasis Area and Severity Index (PASI) was used to evaluate disease severity. A punch biopsy was taken from psoriatic skin lesions (30), perilesional (30) skin, and matched site of controls (20). The pathological and immunostaining assessments of CYR61 were conducted. Results There was a significant gradual progressive overexpression of CYR61 in keratinocytes from control skin to perilesional and lesional psoriatic skin (P = .00). Moreover, lesional psoriatic skin showed overexpression of CYR61 in inflammatory cells in the dermis than controls. CYR61 expression (lesional epidermis) revealed a significant positive correlation with the PASI score (r = .63; P = .00). There was a significant relationship between intensity and H‐core of CYR61 in the lesional psoriatic epidermis with joint affection. Conclusion CYR61 may trigger epidermal hyperplasia and potentiate inflammatory infiltration in psoriasis vulgaris patients, and therapies targeting CYR61 may be effective in the management of psoriasis vulgaris.
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