The Relation between Skin Interleukin23 (IL23) and PsoriaticMusculoskeletal Manifestations

Abstract

soriatic arthritis is a chronic inflammatory autoimmune disease that it is characterized by inflammatory arthritis and skin psoriasis. Though it now recognized as a separate disease entity, yet it is considered as a part of the seronegative spondyliarthropathy family. This disease affects musculoskeletal structures including skin, nails, joints, enthuses, synovial sheathes of tendons and axial skeleton. The clinical course of PsA is unpredictable, evidence indicates that it can be debilitating condition that leads to increased morbidity and mortalitity. Psoriatic arthritis is a potentially damaging and destructive disease, it has a significant impact on functional impairement, joint damage as well as quality of life which emphasize on the importance of improving assessment and management of the disease as radiographic damage can occur within 2 years of disease onset in almost half of patients with PsA and the disease follows a chronic progressive course of most of patients. Overexpression of proinflammatory cytokines as IL23, IL17, is the most striking feature of PsA. IL23 is a proinflammatory cytokine which belongs to IL12 family. It is heterodimeric protein composed of two subunits p19 and p40 which are linked by disulfide bond. P19 subunit is unique component of IL23, where p40 subunit is shared by IL23 and IL12. IL23 is essential in bridging the innate and adaptive immune response through binding of IL23 to IL23 receptor which triggers differentiation of Th17 cells. IL23/IL17 axis contributes in PsA pathogenesis through activation of keratinocytes, neutrophils, osteoclasts and their presence in psoriatic skin, synovial fluid of joints and enthuses. Musculoskeletal ultrasound (MSUS) has been used for several years to assess joint pathology and may have utility in assessment of disease activity in patients with joint inflammatory disease as PsA. The use of high frequency transducers provided excellent tissue resolution, better understanding of inflammation of jonts and adjacent synovial structures. The role of ultrasound has not been limitedin to assessment of joint pathology in PsA but also it has been expanded to include the assessment of subclinical affection and its possibility in using US as an outcome measure in patients with PsA. This thesis was carried out to study the expression of IL23 in psoriatic lesion and its relation with skin inflammation and whether its presence is related with musculoskeletal (joints and enthuses) inflammatory process in order to evaluate its possible role in both pathogenesis and early prediction of psoriatic arthropathy. We conduct our study on 20PsA patients with musculoskeletal manifestations, 20 psoriatic patients with skin manifestations only and 20 normal healthy subjects serving as a control group. All patients and control group were subjected to history taking, clinical examination, laboratory investigations, plain x ray of affected joints, skin biopsy specimen and MSUS of DIP joints, knee joints and over enthuses of lower limbs. The present study revealed that: • Statistically high significant correlation between dermal inflammation and each of IL23 epidermal and dermal keratinocytes in both PsA and psoriasis groups • No correlation between hyperkeratosis and each of IL23 epidermal and IL23 dermal keratinocytes in PsA group. • Statistically significant correlation between hyperkeratosis and IL23 epidermal keratinocytes. Statistically high significant correlation between hyperkeratosis andIL23 dermal keratinocytes in psoriasis group.