EBIO - Enthesitis Biopsy Study

Psoriatic arthritis (PsA) is a heterogeneous inflammatory rheumatologic disorder characterized by inflammatory arthritis, enthesitis, dactylitis and spondylitis, affecting 6% to 39% of the patients suffering from psoriasis. The exact prevalence of PsA is unknown. Estimates of incidence vary from 0.3% to 1% of the population. Disease onset typically occurs between the ages of 30 and 55 years, and affects both genders equally. PsA is classified as a seronegative spondyloarthropathy (SpA) because it shares certain features with other conditions included in that group. Indeed, spinal involvement has been reported in approximately 50% of patients with PsA. In addition, PsA is associated with enthesitis and dactylitis, which are extra-articular features common to SpA. Finally, the majority of patients with PsA are negative for the rheumatoid factor. Recent studies have challenged the assertion that PsA is a more benign disease than rheumatoid arthritis. There is an increasing body of evidence that suggests that PsA patients experience progressive joint destruction over a relatively short period of time. The results from these studies indicate that PsA is erosive and deforming in nearly half of the patients, with joint damage appearing in the first years of disease onset. Other investigators later confirmed that 41% of the patients developed erosive disease within 2 years of onset of symptoms.

Diagnosis and treatment as early as possible has become the standard of care in rheumatoid arthritis in order to prevent disease progression, irreversible functional impairment and premature death. Since the 1970s, it has also been recognized that each inflammatory lesion (joint synovitis, tenosynovitis, dactylitis, enthesitis, sacroiliitis, and spondylitis) can develop without symptoms or signs that are recognizable by the patient and the physician. Such patients can be considered to have subclinical or "occult" PsA. Support for this notion comes from imaging studies providing evidence for the existence of subclinical inflammatory changes in patients with psoriatic skin disease using MRI or high-resolution ultrasound scans.

The investigators focused on the concept of "pre-clinical" changes in their own observational study. Patients suffering from psoriasis with no present or past signs of joint manifestations to stringently rule out clinical joint involvement, have been investigated. The investigators recently described that patients with psoriasis, but without PsA, exhibit entheseophytes as the result of pathological bone formation in the joints as a pathological hallmark of PsA. Recent work has identified enthesial pathology as a specific part of the PsA disease process. Entheses may represent the primary site of musculoskeletal changes in psoriasis patients developing PsA. In particular, the understanding of enthesial structures as an organ with a high degree of structural and functional organisation and the coining of the term 'synovio-entheseal complex' have extended the view on PsA. These concepts are of potential importance in searching for the discrete changes of the joints in patients with psoriatic skin disease. This finding reinforces the pathophysiological role of the entheses in patients with psoriatic disease. Apparently, enthesial changes can occur in the sole presence of skin disease and do not require the clinical arthritis corroborating the concept of an intrinsic clinical connection between the skin and the entheses, which has been previously suggested by molecular studies referring to the role of interleukin-23 as a linker between skin and enthesial pathology.

In the peripheral joints, entheses can be found at the attachment of the collateral ligaments and the circumferential insertion of the capsule itself, which are also known as 'synovio-entheseal complexes' and are highly prone to structural bone changes. Furthermore, functional entheses exist at the dorsal and palmar sites of the MCHs serving as pulleys for the extensor and flexor tendons, respectively. Importantly, these mechanically exposed locations were identical with the sites of new bone formation, suggesting a tight connection between mechanical factors and the bone response observed in psoriasis patients.

Findings provide new evidence for the existence of a Deep Koebner Phenomenon at the enthesial sites in psoriasis patients. In its original description, this phenomenon corresponds to the trigger of inflammation and acro-osteolysis by a discrete traumatic injury. New findings extend the concept of the Deep Koebner Phenomenon suggesting a pathological tissue response to mechanical stress in psoriasis patients. This response affects the mechanically exposed sites of the body, which are the skin and the entheses. The specific importance of entheseophyte formation in psoriasis patients is also supported by the observation that the burden of bone erosions was not significantly enhanced in psoriasis patients compared with healthy controls.