[Digitally supported rheumatological screening consultation : How useful is a questionnaire scoring system (RhePort)?] / Digital unterstützte rheumatologische Screeningsprechstunde : Wie hilfreich ist ein Fragebogen-Scoringsystem (RhePort)?

Regarding scarce capacities an early detection consultation (EDC) was established to discriminate patients in an outpatient setting with inflammatory from non-inflammatory rheumatic diseases. A total of 500 patients suspected of having a rheumatic disease received an appointment within 2 weeks. They were interviewed with the help of a digital questionnaire (RhePort), briefly physically examined followed by a determination of CRP. The questionnaire answers were scored using an algorithm within RhePort (from 0 = non-inflammatory to 4 = highly probably inflammatory). Likewise, after completion of the EDC, the rheumatologists scored the overall assessment. The RhePort score and EDC score were compared with the "true" diagnosis made in a detailed second examination after an average of 10 weeks. In 490 evaluable patients 133 inflammatory (27%) and 357 noninflammatory rheumatic diseases (73%) were diagnosed. A classification based solely on the RhePort questionnaire (score > 1) identified 103 out of 129 as inflammatory (sens. 80%) and 125 out of 355 as non-inflammatory (spec. 35%) resulting in an AUC of 0.62 after ROC analysis. With a score > 1, the rheumatological assessment after EDC classified 130 out of 133 patients as inflammatory (sensitivity 98%) and 261 out of 357 as non-inflammatory (specificity 73%). The combined EDC can decisively increase the sensitivity and specificity compared to an "automated" survey by means of a digital questionnaire alone. In addition to the early identification and treatment of inflammatory patients, rapid identification of patients who are not in need of rheumatological treatment can create capacities for care.

Decrease in circulating endothelial cell adhesion molecule and thrombomodulin levels during oral iloprost treatment in rheumatoid arthritis patients: preliminary results.

OBJECTIVE: Rheumatoid arthritis is a chronic inflammatory autoimmune disease with proinflammatory cytokines involved in its pathogenesis. Recently in vitro as well as in vivo studies have shown that iloprost, a stable prostacyclin analogue, can reduce the release of these cytokines. This study was performed to further investigate the anti-inflammatory effects of iloprost by determining plasma adhesion molecules as markers of endothelial cell activation, and plasma thrombomodulin as a parameter of endothelial cell injury in patients with rheumatoid arthritis receiving oral iloprost therapy. METHODS: Plasma thrombomodulin levels and the values of the plasma adhesion molecules VCAM-1 (vascular cell adhesion molecule 1), E-selectin (CD62E), and ICAM-1 (intercellular adhesion molecule 1, CD 54) were measured by ELISA during a 7-day period of treatment with orally-administered iloprost in 14 patients with active rheumatoid arthritis. Finally, the same parameters were determined at the end of the observation period (1 week after the end of therapy). In addition, the disease activity was measured using the DAS (disease activity score) as well as the patients' self-assessed pain severity, and correlated with the changes of plasma adhesion molecule and thrombomodulin levels. RESULTS: The plasma levels of all three adhesion molecules as well as of thrombomodulin significantly decreased under therapy with oral iloprost. After 1 week (day 7 of therapy), the mean percent changes from day 0 were -20.1% for VCAM-1 (p = 0.008), -21.2 for ICAM-1 (p = 0.003), -24.6% for E-selectin (p = 0.001), and -21.7% for thrombomodulin (p = 0.003). This decrease lasted up to 1 week after the end of therapy in the case of VCAM-1 (p = 0.023) and ICAM-1 (p = 0.001). Further analysis of the results revealed additional significant correlations between different parameters of clinical disease activity, thrombomodulin and adhesion molecules. CONCLUSION: This study showed hints towards clinical effects in patients with rheumatoid arthritis receiving oral iloprost therapy. Pathophysiologically, the decrease of adhesion molecules points at an immunomodulating effect of iloprost. The observed thrombomodulin-lowering effect of iloprost may indicate stabilisation of endothelial cell function by diminishing endothelial cell injury.

A 7-day oral treatment of patients with active rheumatoid arthritis using the prostacyclin analog iloprost: cytokine modulation, safety, and clinical effects.

OBJECTIVE: The purpose of this study was to investigate the plasma levels of tumor necrosis factor (TNF)-alpha, its soluble p55 and p75 receptors, ex vivo lipopolysaccharide (LPS)-stimulated TNF-alpha production, and plasma levels of interleukin 6, interleukin 1, and interleukin 10 during a 7-day oral administration of iloprost in patients with active rheumatoid arthritis. METHODS: During oral 7-day administration of the prostacyclin analog iloprost, the plasma levels of TNF-alpha, soluble p55, and p75 TNF-alpha receptors, IL-1, IL-6, and IL-10 and C-reactive protein (CRP) in serum were determined on days -1, 1, 3, 4, 6, and 8 and after a treatment-free follow-up on day 15. In addition, the ex vivo TNF-alpha production in whole blood under LPS-stimulated and -unstimulated conditions were measured. Fifteen patients with active rheumatoid arthritis and baseline TNF-alpha plasma levels of > or =2 pg/ml were included in independent groups receiving 50 microg, 100 microg, or 150 microg iloprost per day in addition to their conventional antirheumatic therapy. The respective dose was given once daily from days 1 to 3 and doubled from days 4 to 7. The tender and swollen joint count (28 joints) and the patients' assessments of pain severity and general feeling (10-cm visual analog scale) were performed on days -1, 4, and 8 (end of treatment) and after a 7-day follow-up. RESULTS: The patients showed decreased TNF-alpha levels during iloprost administration. The decrease in the ex vivo LPS-stimulated TNF-alpha production and plasma levels of the p75 TNF receptor were found to be associated with a decrease in the number of tender joints. Additionally, IL-6 was downregulated. CONCLUSION: A 7-day oral administration of iloprost resulted in a change of in vivo and ex vivo cellular cytokine production, with reductions in TNF-alpha and p75 TNF receptor plasma levels. These changes were associated with clinical improvements in active rheumatoid arthritis.