Newly diagnosed seropositive rheumatoid arthritis in a 52-year-old man superimposed on long-standing ankylosing spondylitis during secukinumab treatment.

Rheumatoid arthritis (RA) and ankylosing spondylitis (AS) are severe chronic inflammatory joint diseases with different immune-mediated mechanisms playing a role in their pathogenesis. Rheumatoid arthritis is an erosive arthritis of peripheral joints and AS is a spondyloarthropathy affecting mainly sacroiliac and spinal joints leading to excessive bone formation and ankylosis. The coexistence of RA and AS in the same patient is rare. Presented here is a 52-year-old patient with long-standing AS with bilateral ankylosis of sacroiliac joints who developed peripheral symmetric polyarthritis while being treated with the interleukin 17 inhibitor secukinumab introduced due to secondary inefficacy of the tumor necrosis a inhibitor etanercept. He was finally diagnosed with seropositive RA coexisting with AS and treatment was changed to the Janus kinase inhibitor tofacitinib. Eventually, remission was sustained with use of the interleukin 6 inhibitor tocilizumab. This is the first case of RA developing during anti-interleukin 17 therapy. Although tocilizumab lacks efficaciousness in AS, in this case therapy was succesful as the RA-driving cytokine mechanism possibly prevailed.

Blood monocyte heterogeneity and markers of endothelial activation in ankylosing spondylitis.

OBJECTIVE: Ankylosing spondylitis (AS) is associated with excessive cardiovascular (CV) morbidity. Interactions between activated endothelium and monocytes precede atherosclerotic plaques. Our aim was to quantify blood monocyte subsets in relation to endothelial activation and inflammatory activity in subjects with AS who were free of clinical atherosclerotic CV disease. METHODS: Markers of inflammation and endothelial activation were measured in 47 patients with AS receiving no disease-modifying antirheumatic drugs, and 22 healthy controls. Exclusion criteria included atherosclerotic CV disease and traditional risk factors. Flow cytometry was used to identify monocyte subsets: classical CD14(++)CD16(-), intermediate CD14(++)CD16(+), and nonclassical CD14(+)CD16(++) monocytes and to evaluate their expression of CD11b and CD11c. RESULTS: Traditional risk factors were comparable among the groups, except for lower high-density lipoprotein cholesterol in AS (p = 0.007). Relative to controls, in subjects with AS counts of classical monocytes were higher (84.3 ± 5.4 vs 78.9 ± 5.3% of blood monocytes, p < 0.001) and nonclassical monocytes lower (2.9 ± 2.2 vs 5.5 ± 2.3%, p < 0.001). In AS we observed increased soluble intercellular adhesion molecule-1 [251 (224-293) vs 202 (187-230) ng/ml, p = 0.002], an endothelial ligand for monocytic ß2-integrin CD11b/CD18. CD11b expression on all 3 monocyte subsets was elevated in 21 AS subjects with a Bath Ankylosing Spondylitis Disease Activity Index score ≥ 4 versus the remaining patients (p = 0.005-0.03). C-reactive protein, interleukin 6 (IL-6), and pentraxin-3 were increased in AS, in contrast to tumor necrosis factor-α and IL-18. IL-6 correlated with classical monocytes numbers in AS (r = 0.56, p < 0.0001) but not in the controls (r = 0.10, p = 0.65). CONCLUSION: Our findings suggest a contribution of immune dysregulation to enhanced monocyte-endothelial interactions in AS, especially in patients with active disease, which possibly can accelerate atherogenesis on a longterm basis.