Introduction Vitiligo is an autoimmune disease of the skin that targets pigment producing melanocytes and results in patches of depigmentation that are visible as white spots (Frisoli et al., 2020) Vitiligo is a relatively common acquired pigmentation disorder that can cause significant psychological stress (Leung AKC et al., 2021). The disease affects both genders equally, it can appear at any age, and the average age of onset is somewhat variable in different geographic (Majumder et al, 1993), with an estimated prevalence of 0.5-2% of the population in both adults and children worldwide (Krüger et al, 2012).

Vitiligo results in white macules and patches on the body. Initial lesions occur most frequently on the hands, forearms, feet, and face, favoring a periocular or perioral distribution (Ahmed jan N et al., 2023). Vitiligo lesions are classified into 2 major categories: segmental vitiligo (SV) and non-segmental vitiligo (NSV) (Relke et al ., 2019). Segmental vitiligo is characterized by its early onset, rapid stabilization, and unilateral distribution (Van Geel et al., 2017). Non-segmental vitiligo comprises of generalized (vitiligo vulgaris), acrofacial, mucosal (multifocal), and universal vitiligo (Kovacevic et al., 2016). Non-segmental vitiligo (NSV) is the most common form of vitiligo (Benzekri et al., 2013). Multiple mechanisms are involved in melanocyte disappearance, namely genetic predisposition, environmental triggers, metabolic abnormalities, impaired renewal, and altered inflammatory and immune responses (Boniface K et al ., 2018).

The results of some studies indicate a frequent association of vitiligo with autoimmune diseases. A number of studies have established a higher prevalence of autoimmune endocrine diseases in women, as well as in non-segmental vitiligo patients and in cases of family history of vitiligo and/or other autoimmune diseases. In addition, it was shown that the prevalence of endocrine diseases increases with increasing area of depigmentation (Troshina EA et al., 2020). Autoimmunity in vitiligo is driven by the IFN-γ-CXCL10 cytokine signaling pathway. Activated melanocyte-specific CD8+ T cells secrete IFN-γ, which signals through the IFN-γ receptor (IFN-γR) to activate JAK1/2 and STAT1. This induces the production of CXCL9 and CXCL10, which signal through their receptor CXCR3 to recruit more auto-reactive T cells to the epidermis, resulting in widespread melanocyte destruction (Harris JE et al., 2017).

The lysosomal cysteine proteinases of the papain family are involved in lysosomal bulk proteolysis, major histocompatibility complex class II-mediated antigen presentation, pro-hormone processing, and extracellular matrix remodeling.

Inclusion Criteria:

• Patients with non-segmental vitiligo attending the dermatology outpatient clinics of Sohag University hospital. A group of age and sex- matched healthy participants will be included as a control group.

Exclusion Criteria:

• (A) Pregnancy and lactation. (B) Patients on topical and systemic treatment for vitiligo in the last 4weeks prior to enrollment in the study.

(C) Malignacies. (D) Patients with systemic diseases, diabetes, hypertension and bleeding disorders.

(E) Patients who are receiving chemotherapy or radio therapy.