Association of Serum Calprotectin (S100A8/A9) Level With Disease Relapse in Proteinase 3-Antineutrophil Cytoplasmic Antibody-Associated Vasculitis.

OBJECTIVE: S100A8/A9 (calprotectin) has shown promise as a biomarker for predicting relapse in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV). This study was undertaken to investigate serum S100A8/A9 level as a biomarker for predicting future relapse in a large cohort of patients with severe AAV. METHODS: Serum levels of S100A8/A9 were measured at baseline and months 1, 2, and 6 following treatment initiation in 144 patients in the Rituximab in ANCA-Associated Vasculitis trial (cyclophosphamide/azathioprine versus rituximab [RTX] for induction of remission) in whom complete remission was attained. RESULTS: Patients were divided into 4 groups: proteinase 3 (PR3)-ANCA with relapse (n = 37), PR3-ANCA without relapse (n = 56), myeloperoxidase (MPO)-ANCA with relapse (n = 6), and MPO-ANCA without relapse (n = 45). Serum S100A8/A9 level decreased in all groups during the first 6 months of treatment. The percentage reduction from baseline to month 2 was significantly different between patients who experienced a relapse and those who did not in the PR3-ANCA group (P = 0.046). A significantly higher risk of relapse was associated with an increase in S100A8/A9 level between baseline and month 2 (P = 0.0043) and baseline and month 6 (P = 0.0029). Subgroup analysis demonstrated that patients treated with RTX who had increased levels of S100A8/A9 were at greatest risk of future relapse (P = 0.028). CONCLUSION: An increase in serum S100A8/A9 level by month 2 or 6 compared to baseline identifies a subgroup of PR3-ANCA patients treated with RTX who are at higher risk of relapse by 18 months. Since RTX is increasingly used for remission induction in PR3-ANCA-positive patients experiencing a relapse, S100A8/A9 level may assist in identifying those patients requiring more intensive or prolonged treatment.

Factors Determining the Clinical Utility of Serial Measurements of Antineutrophil Cytoplasmic Antibodies Targeting Proteinase 3.

OBJECTIVE: Relapse following remission is common in antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (AAV), particularly with ANCAs directed at proteinase 3 (PR3). This study was undertaken to evaluate the association of an increase in PR3-ANCA level with subsequent relapse. METHODS: Data from the Rituximab versus Cyclophosphamide for ANCA-Associated Vasculitis (RAVE) trial were used. Starting from the time of achieving complete remission, serial measurements by direct and capture enzyme-linked immunosorbent assays (ELISAs) were analyzed in 93 patients with PR3-ANCA, using Cox proportional hazards regression. RESULTS: An increase in PR3-ANCA level was identified in 58 of 93 subjects (62.4%) by direct ELISA and in 59 of 93 (63.4%) by capture ELISA. Relapses occurred in 55 of 93 subjects (59.1%), with 25 and 21 occurring within 1 year after an increase by direct ELISA and capture ELISA, respectively. An increase by direct ELISA was associated with subsequent severe relapses (hazard ratio [HR] 4.57; P < 0.001), particularly in patients presenting with renal involvement (HR 7.94; P < 0.001) and alveolar hemorrhage (HR 24.19; P < 0.001). Both assays identified increased risk for severe relapse in the rituximab group (HR 5.80; P = 0.002 for direct ELISA and HR 4.54; P = 0.007 for capture ELISA) but not the cyclophosphamide/azathioprine group (P = 0.103 and P = 0.197, respectively). CONCLUSION: The association of an increase in PR3-ANCA level with the risk of subsequent relapse is partially affected by the PR3-ANCA detection methodology, disease phenotype, and remission induction treatment. An increase in PR3-ANCA level during complete remission conveys an increased risk of relapse, particularly severe relapse, among patients with renal involvement or alveolar hemorrhage and those treated with rituximab. Serial measurements of PR3-ANCA may be informative in this subset of patients, but the risk of relapse must be weighed carefully against the risks associated with therapy.

Complete response to steroids in dural inflammatory pseudotumor associated with Still's disease.

We report a unique case of a dural-based inflammatory pseudotumor (IPT) arising in the left cavernous sinus of a patient with a history of juvenile Still's disease. The patient presented with hemi-facial paresthesias, dull, constant headaches, and transient episodes of sharp pain along the temporalis region. Treatment with oral steroid therapy resulted in complete regression of the lesion and accompanied neuralgia symptoms. Because intracranial IPT can mimic meningiomas both clinically and radiographically and can be associated with systemic arthritic diseases, neurosurgeons should be familiar with this entity in order to avoid unnecessary radical surgery and alternatively consider a tapering course of steroid therapy.