# Understanding the Intricate Pathophysiology of Psoriasis and Related Skin Disorders
## 4 Sporiasis and Associated Dermatologic Disorders
In psoriasis, granzyme B contributes to the inflammatory processes and the proliferation of skin cells, exacerbating the disease's characteristic symptoms such as scaling and redness. In AA, it is involved in the destruction of hair follicles, resulting in the characteristic patchy hair loss. Both conditions share features of chronic inflammation and immune dysregulation, with granzyme B mediating cellular apoptosis and inflammation in each. In psoriasis, granzyme B drives keratinocyte hyperproliferation and inflammation, whereas in AA, it facilitates autoimmune-mediated follicular destruction. Understanding the role of granzyme B in these conditions may provide insights into common pathogenic mechanisms and potential therapeutic targets for managing these chronic autoimmune skin diseases [9]. Autophagy, a cellular process essential for degrading and recycling damaged organelles and proteins, is important for maintaining skin health and managing various skin diseases, including psoriasis and AA. This process helps preserve the skin barrier by regulating cellular turnover and responding to stress. In psoriasis, impaired autophagy can worsen the disease by failing to control cellular damage and inflammation effectively. This leads to increased keratinocyte proliferation and chronic inflammation, contributing to the development and persistence of psoriatic plaques. In AA, autophagy plays a key role in maintaining hair follicle health. Disruptions in autophagy can affect follicle function and immune responses, potentially worsening hair loss and disease progression. Effective autophagy is necessary for managing cellular stress and preserving follicle integrity, with its dysfunction potentially contributing to the onset and severity of AA [10]. The recent identification of coexisting psoriasis and hidradenitis suppurativa (HS) highlights a potential connection warranting further investigation. While numerous case reports describe the simultaneous occurrence of HS and psoriasis, a definitive causal relationship remains unproven due to the lack of robust epidemiological data. Despite their distinct skin manifestations, both chronic conditions share common risk factors, such as obesity and cigarette smoking, and significantly impact quality of life. Additionally, they involve overlapping inflammatory pathways, including the IL-12/IL-23 axis, IL-17 interactions, and TNF-\(\alpha\)[11]. HS is a chronic autoimmunity skin disease characterized by the inflammation of hair follicles, particularly in areas rich in apocrine glands. Its prevalence varies, estimated to be between 0.7% and 1.2%, with a higher incidence in females. HS typically affects intertriginous regions such as the axillary, submmamary, and inguinal areas, as well as the anogenital region. This condition can subsequently lead to the formation of abscess, sinus tracts, and scarring, profoundly impacting the patient's quality of life. Psoriasis is thought to be triggered in genetically susceptible individuals following a loss of T cell tolerance to specific self-antigens, potentially in response to an environmental insult that activates innate immune cells. For instance, the release of DNA from damagedcells, when complexed with the antimicrobial peptide LL-37, can activate plasmacytoid dendritic cells (pDCs) via TLR-9, leading to the production of IFN-\(\alpha\). This process enables dendritic cells to present LL-37 autoantigens to T cells. These T cells subsequently differentiate into Th1 and Th17 subsets under the influence of specific polarizing cytokines. Th17 cells produce IL-17A, IL-17F, and IL-22, which, alone or in combination with TNF-\(\alpha\), strongly activate keratinocytes. The activated keratinocytes then secrete antimicrobial peptides, cytokines, and chemokines, which recruit and activate additional immune cells, resulting in a feedback loop of persistent inflammation. The key cytokine, IL-23, is the main mediator in activating and maintaining the inflammatory cascade brought about by Th17 and Th22 cells [11].