Rheumatoid arthritis (RA) is a chronic autoimmune disease where the body’s immune system mistakenly attacks the joints, causing ongoing inflammation that progressively damages joint structures over time. This damage unfolds through a complex cascade of immune responses, tissue changes, and structural breakdown that ultimately impairs joint function and causes deformities.
At the core of RA joint damage is inflammation of the synovium, the thin membrane lining the joints. Normally, the synovium produces synovial fluid, which lubricates and nourishes the cartilage and bones inside the joint. In RA, the immune system targets the synovium, triggering an inflammatory response. Immune cells such as helper T cells, including a specialized subset called peripheral helper T (Tph) cells, accumulate in the joint lining and form immune “hubs” or tertiary lymphoid structures. These hubs become sites of ongoing immune activation, where Tph cells stimulate other immune cells like B cells, perpetuating inflammation and tissue destruction[4][5].
This chronic inflammation causes the synovium to thicken and swell, a condition called synovitis. The inflamed synovium produces excess synovial fluid, leading to joint swelling, redness, and pain. Over time, the thickened synovium, now called pannus, aggressively invades and erodes adjacent cartilage and bone. The pannus releases enzymes and inflammatory molecules that break down cartilage, the smooth tissue that cushions bones in the joint, and stimulate osteoclasts, the cells responsible for bone resorption. This results in cartilage degradation and bone erosion, which are central to the loss of joint integrity and function in RA[1][3].
A key factor worsening this damage is the hypoxic (low oxygen) environment within the inflamed joint. Despite new blood vessel formation (angiogenesis) stimulated by hypoxia, these vessels are often abnormal and insufficient to meet the oxygen demands of the rapidly growing pannus tissue. This persistent hypoxia further activates molecular pathways involving hypoxia-inducible factor 1-alpha (HIF-1α), which promotes osteoclast activity and cartilage destruction, accelerating joint damage[3].
As cartilage wears away and bone erodes, the joint loses its smooth surfaces and structural support. Ligaments and tendons around the joint also become inflamed and weakened, reducing joint stability. This combination causes the bones to shift, collapse, or deform, leading to characteristic joint deformities seen in RA. Common deformities include ulnar deviation (fingers drifting toward the pinky side), boutonnière deformity (bent middle finger joint with extended fingertip), swan neck deformity (hyperextended middle joint with flexed fingertip), and changes in the feet such as collapsed arches and curled toes[1].
The damage is progressive and, without treatment, leads to permanent joint deformities, loss of mobility, and disability. However, there is a critical window early in the disease—within the first 3 to 6 months of symptom onset—when aggressive treatment can suppress inflammation, prevent pannus formation, and halt or slow joint destruction. Early diagnosis and intervention are essential to preserving joint function and quality of life[1].
In summary, rheumatoid arthritis damages joints over time through a sustained autoimmune attack on the synovium, causing chronic inflammation, pannus formation, cartilage breakdown, bone erosion, and weakening of supportive tissues. This process leads to joint deformities and impaired function, but timely treatment can interrupt this destructive cycle.