Takayasu arteritis is characterised by disturbances of B cell homeostasis and responds to B cell depletion therapy with rituximab.

UNLABELLED: Introduction Takayasu arteritis (TA) is a large vessel vasculitis involving the aorta and its major branches. T cell-mediated autoimmunity is thought to play a major role in its pathogenesis, while the role of B cells is still unclear. METHODS: B cell subsets in the peripheral blood of 17 patients with TA were analysed and compared with nine patients with active systemic lupus erythematosus (SLE) and nine healthy controls by flow cytometry. Based on these findings, three patients with active refractory TA were treated with B cell depletion therapy (BCDT) using monoclonal anti-CD20 antibodies (rituximab). RESULTS: The absolute number and frequency of peripheral blood CD19(+)/CD20(-)/CD27(high) antibody-secreting cells in patients with active TA was significantly higher than in healthy donors. As in active SLE, the majority of these cells are newly generated plasmablasts which significantly correlated with TA activity. Three patients with active refractory TA and expansion of plasmablasts were successfully treated with BCDT, which resulted in remission. CONCLUSION: Disturbances of B cell homeostasis may be critical in TA. Circulating plasmablasts could be a useful biomarker of disease activity and a tool for selecting appropriate candidates for BCDT. B cells and plasmablasts/plasma cells may therefore represent novel targets for effective therapies for TA.

A case of Erdheim-Chester disease initially mistaken for Ormond's disease.

BACKGROUND: A 54-year-old man presented with fever, abdominal pain, anemia, elevated C-reactive protein level and decreased renal function. Idiopathic retroperitoneal fibrosis (Ormond's disease) had been diagnosed in the past, leading to surgical ureterolysis. Re-evaluation of the CT scans and histological biopsy samples revealed unusual sclerosis of the long bones and diffuse infiltrates of foamy histiocytes in the bone marrow and the retroperitoneum. INVESTIGATIONS: Physical examination, laboratory tests including hemoglobin concentration, erythrocyte sedimentation rate, C-reactive protein level, beta2-microglobulin level, creatinine level, CT of the chest and abdomen, bone scintigraphy, bone marrow and soft tissue biopsies and immunohistochemistry. DIAGNOSIS: Erdheim-Chester disease with retroperitoneal fibrosis and bone sclerosis. MANAGEMENT: Treatment with glucocorticoids failed. The patient's symptoms improved significantly after initiation of interferon-alpha therapy.

Correlation of different bone markers with bone density in patients with rheumatic diseases on glucocorticoid therapy.

Osteoporosis is a common concomitant disease in patients with rheumatic diseases on glucocorticoid (GC) therapy. Bone status is usually evaluated by determination of bone density in combination with clinical examinations and laboratory tests. However, the strength of individual biochemical bone makers in GC-induced osteoporosis has yet to be fully clarified. For this reason, different bone markers were investigated in correlation with bone density in patients with rheumatic diseases. Approximately 238 patients (212 women, 26 men) with a rheumatic disease and under GC therapy were examined consecutively for the first time with regard to bone density (BMD) and bone markers [osteocalcin, bone-specific alkaline phosphatase (precipitation method/tandem-MP ostase), crosslinks [pyridinoline (PYD), deoxypyridinoline (DPX), N-terminal telopeptide (NTX)]]. The daily glucocorticoid dose was 10 mg prednisone equivalent (median), and the cumulative dose was 12 g prednisone equivalent (median). None of the patients had previously taken medication for osteoporosis. Osteoporosis was demonstrated in 35.3% of the patients, osteopenia in 47.5%, and a normal BMD in 17.2%. The results of tandem-MP ostase correlated with the BMD of the lumbar spine and of the femoral neck. The values for N-terminal telopeptide and pyridinoline correlated only with the bone density of the femoral neck. All results were statistically significant, although the correlation coefficients were low. After classification of the patients according to their BMD values (osteoporosis, osteopenia and normal BMD), there were significantly more patients with bone markers above the norm in the osteoporosis group and in the osteopenia group than in the group with normal bone density. All bone markers recorded behaved similarly in relation to the bone density values. The same analysis was also undertaken for the different disease groups. In these subgroups there was also a correlation between ostase/crosslinks with BMD, but the correlation coefficients were low. A general recommendation for the routine use of a specific bone marker in patients with rheumatic diseases on glucocorticoid therapy cannot be made from a cost-benefit point of view mainly because of limited predictive power (low correlation coefficients, incomplete correlation with different sites of BMD measurement).