Nailing down the Genetic and Immunological Basis for Psoriatic Disease

Abstract

Psoriatic disease encompassing skin, joint and nail involvement is largely viewed as autoimmune – a finding supported by data from animal models, the human leucocyte antigen (HLA)-Cw6 disease association in man, T-lymphocyte infiltration in lesional skin and the favourable skin response to T-cell-directed therapies. However, this immunopathogenetic model only applies to the skin, as recent studies failed to demonstrate a HLA-Cw6 association with the nails or joints. Furthermore, the nails and joints are intimately associated with inflammation at points of ligament or tendon insertion (i.e., enthesitis), so it is now appreciated that both of these sites also share a common microanatomical basis. Moreover, inflammation at insertion sites and nails does not appear to be associated with a particular antigenic territory but is quite diffuse in nature. This suggests that an aberrant response to tissue stressing of the integrated nail-joint apparatus, rather than autoimmunity, is driving the inflammatory process. Therefore, HLA-Cw6-associated type 1 psoriasis is more closely linked to autoimmunity, whereas nail and joint disease may be linked to tissue-specific factors, including tissue biomechanical stressing and microtrauma, that lead to activation of aberrant innate immune responses. These observations that stem from nail disease point toward a relative differential involvement of adaptive and innate immunity in the psoriatic disease spectrum and offer a fresh perspective on the pathophysiology of psoriatic disease and how it can be classified along the immunological disease continuum of self-directed inflammation.

Nail Psoriasis Successfully Treated with Intralesional Methotrexate: Case Report

“…McGonagle et al [11 ]reported that T-cell-mediated immunity is predominant in skin lesions and innate immune responses may have a key role, especially in nail and joint involvement of the psoriatic patients. In this respect, the anti-inflammatory MTX seems to be more effective than the T-cell-inhibiting cyclosporine in nail psoriasis [11]. …”

Efficacy of Ustekinumab in Nail Psoriasis and Improvement in Nail-Associated Quality of Life in a Population Treated with Ustekinumab for Cutaneous Psoriasis: An Open Prospective Unblinded Study

“…Furthermore, recent imaging, histological and genetic studies have suggested a new link between joint and nail disease. Frequent microdamage and tissue repair at normal enthesis attachment sites in healthy joints has resulted in a proposed new model of psoriatic arthritis pathogenesis embracing the concept of autoinflammation, whereby tissue-specific factors, including microtrauma, lead to regional innate immune activation and persistent inflammation, as an alternative to primary immunopathology driven by T and B cell abnormalities [8,9]. If such is the case, early treatment of severe nail disease might offer additional benefit to the patient by diminishing joint inflammation.…”

Linear Pitting and Splinter Haemorrhages Are More Commonly Seen in the Nails of Patients with Established Psoriasis in Comparison to Psoriatic Arthritis

“…Nail involvement in psoriasis may have two basic patterns, one related to epidermal changes such as subungual hyperkeratosis and a second pattern that might be associated with the entheses that anchor the nail matrix and nail plate region [15]. In the latter case, we hypothesised that the involvement of the nail matrix by the inflammatory process might contribute to lesions such as pitting in a linear pattern consistent with the ‘finger-like’ attachment of the ligamentous structures linking the nail to the extensor tendon and distal interphalangeal joint capsule [16].…”