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Abstract Acne vulgaris, a chronic inflammatory disease of the pilosebaceous unit, is the most common cutaneous disorder worldwide affecting up to 80% of adolescents and up to 50% of adults. It is characterized by inflammatory papules, pustules, open and closed comedones, cysts and nodules. Acne pathogenesis begins with abnormal keratinization that causes impaction and distension of the lower portion of the infundibulum, forming the comedone. Other factors include a complex interplay among sebum production, with changes in lipid composition, hypersensitivity to androgen stimulation, Propionibacterium acnes, and local inflammatory cytokines elaborated by the innate immune system. Reactive oxygen species released from the impacted damaged follicular walls are thought to be the reason for the progress of the inflammation in the pathogenesis of the disease. Nuclear factor erythroid 2-related factor 2 (NRF2) is a transcription factor that in humans is encoded by the NFE2L2 gene. It is a basic leucine zipper (bZIP) protein that regulates the expression of antioxidant proteins that protect against oxidative damage triggered by injury and inflammation. The current study aimed at evaluation of the possible role of NRF2 in the pathogenesis of acne vulgaris through its immunohistochemical assessment in inflammatory and non inflammatory acne compared to normal skin in addition of correlating NRF2 expression with the clinical and pathological parameters of acne. The study was carried out on thirty patients with acne vulgaris (AV) and 30 age and sex matched healthy volunteers as a control group. They were selected from the Dermatology Outpatient Clinic, Faculty of Medicine, Menofia University. All participants were subjected to complete history taking and dermatological examination through grading of acne. Three millimeters punch biopsy was taken from each patient (inflammatory and non inflammatory) acne lesions of the arms, upper trunk and back under deeply infiltrated local anesthesia. The biopsies were processed in Pathology Department, Faculty of Medicine, Menoufia University. from each block, 2 sections were cut, one was stained by haematoxylin and eosin for routine histopathological examination, and the other one was stained immunohistochemically for the evaluation of NRF2 expression. Nrf2 was upregulated in cases than controls. This was demonstrated by higher expression positivity, intensity and H score in cases (follicular, perifollicular epidermis and dermis) than in controls. Also, the nuclear expression was higher in cases than in controls. Regarding epidermal expression of Nrf2 in the perifollicular epidermis, There were higher positivity, Nuclear localization, intensity and H score in cases than controls and in inflammatory than both (non inflammatory and control groups). There were significant correlation between NRF2 expression positivity in the perifollicular epidermis and early onset age, type of acne lesion (more in inflammatory than comedonal), inflammatory severity (increased with increased severity), perivascular inflammatory location and with inflammatory infiltrate (neutrophils, plasma cells and histiocytes). Summary 65 There were significant correlation between NRF2 expression positivity in the follicular epidermis and early onset age, type of acne lesion (more in inflammatory than comedonal), inflammatory severity (increased with increased severity), perivascular inflammatory location and with inflammatory infiltrate (plasma cells, histiocytes and lymphocytes). Nuclear H score of the perifollicular epidermis was correlated to age of onset with high H score was associated with the younger age of onset, type of acne lesion (more in inflammatory than comedonal) inflammatory severity (increased with increased severity), perivascular inflammatory location and with inflammatory infiltrate (neutrophils, plasma cells and histiocytes). Cytoplasmic H score of the perifollicular epidermis was correlated to age of onset with high H score was associated with the younger age of onset, type of acne lesion (more in inflammatory than comedonal) inflammatory severity (increased with increased severity), periadnexal inflammatory location and with inflammatory infiltrate (neutrophils). Nuclear H score of the follicular epidermis was correlated to age of onset with high H score was associated with the younger age of onset, type of acne lesion (more in inflammatory than comedonal) inflammatory severity (increased with increased severity), periadnexal inflammatory location and with inflammatory infiltrate (neutrophils, plasma cells and histiocytes). Cytoplasmic H score of the follicular epidermis was correlated to type of acne lesion (more in inflammatory than comedonal) and less with inflammatory infiltrate (plasma cells). |