Translational perspectives on psoriatic arthritis

Abstract

The term psoriatic disease encompasses the array of disorders (arthritis, inflammatory bowel disease, uveitis, obesity, metabolic syndrome, type II diabetes, and cardiovascular disease) that are associated with psoriasis. Psoriatic arthritis (PsA) is present in about 25% of patients with psoriasis; in most cases, the psoriasis precedes joint disease by about 10 years. Previous studies revealed that osteoclast precursors (OCP) are elevated in PsA and that the frequency of these circulating cells correlates with bone destruction. More recently OCP were found to be increased also in early rheumatoid arthritis and in 25% of psoriasis patients without arthritis. Bone marrow edema, observed on magnetic resonance imaging, in PsA represents infiltration of underlying marrow with inflammatory cells based on studies in transgenic tumor necrosis factor (TNF) arthritis murine models. Studies in the TNF transgenic mouse model also revealed that changes in lymph node volume precede joint flare. These translational studies point to potential biomarkers of arthritis in psoriasis patients and generate alternative hypotheses to explain the events that lead to arthritic flare.

Figure 1.

Pathways that link skin and joint inflammation in PsA. Events that begin in the skin or the bone marrow result in activation of T lymphocytes and monocytes (immunocytes) that circulate to the joint. A second event in the joint (e.g., trauma, activation of Toll receptors by pathogens) triggers synovitis, which is modulated by events in the draining lymph node and the bone marrow. Circulating and resident monocytes undergo differentiation to dendritic cells (DC) and macrophages (Mϕ) in the skin. Similar differentiation programs unfold in the joint but monocytes can also mature into osteoclasts (OC), an event not observed in the skin.

Figure 2.

Lymph node dynamics and joint inflammation. Radiology and histology of a knee joint from a representative 5-month-old tumor necrosis factor–transgenic (TNF–Tg) mouse (panels ABD) and its wild type (WT) littermate (panels EBH). Post contrast magnetic resonance images show enhancing synovium (arrows). Bone marrow edema is present in the TNF–Tg mouse, as indicated by the high signal intensity in the bone marrow space (panel A), but is absent in the WT mouse (panel E). Corresponding 3 dimensional reconstructions and calculated synovial (white) and popliteal lymph node (black) volumes (panels B and F) are also shown. Differences in these quantitative imaging biomarkers are validated in the corresponding orange GBAlcian blue–stained histology sections (4× original magnification; panels C and G); boxed areas of C and G are shown at 200× original magnification (D and H, respectively). The TNF –Tg mouse displays thickened synovial lining (#) and infiltration into subchondral bone (arrowhead). Panels I and J: disease progression in TNF–Tg and WT mice as a function of synovial volume (I) and lymph node volume (J). From Proulx ST, et al. Arthritis Rheum 2008;58:2019-29; with permission.