Plasma fibrinogen along with patient-reported outcome measures enhances management of polymyalgia rheumatica: a prospective study.

OBJECTIVE: We sought to prospectively examine the responsiveness of a number of patient-reported outcome (PRO) measures in polymyalgia rheumatica (PMR), as well as their relationship to the biomarkers erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and plasma fibrinogen. METHODS: Sixty patients with PMR were divided into active (n = 25) or inactive (n = 35) disease groups based on symptoms; physician assessment; and the biomarkers ESR, CRP, and plasma fibrinogen. Groups underwent assessment at baseline and 6 weeks. Disease activity measures and relevant PRO measures were recorded. Measures of responsiveness were compared for all PRO and biomarkers. RESULTS: Visual analog scale disease activity (VASDA) and VAS quality of life (VASQOL) are more responsive to change in disease activity than VAS pain, morning stiffness, Health Assessment Questionnaire (HAQ), and PMR-activity score (AS). Analysis of PMR-AS versus VASDA, VASQOL, and HAQ showed correlation coefficients of 0.87 (p < 0.001), 0.80 (p < 0.001), and 0.68 (p < 0.001), respectively. Receiver-operating curve (ROC) analysis revealed VASDA to be more specific than either HAQ (0.95 vs 0.85; p < 0.001) or VASQOL (0.95 vs 0.93; p < 0.001) for the detection of response to treatment in active PMR. Overall, fibrinogen showed superior correlation coefficients with the various PRO than either of the standard biomarkers ESR or CRP. In addition, standardized response means for fibrinogen, ESR, and CRP were 1.63, 1.2, and 1.05, respectively, indicating that plasma fibrinogen was the most responsive biomarker for assessment of change in disease activity. CONCLUSION: VASDA and VASQOL are the most responsive PRO to changes in disease activity in PMR. In addition, plasma fibrinogen demonstrated greater responsiveness to changes in disease activity and superior correlation with the various PRO measures recorded than did the standard biomarkers ESR and CRP.

Plasma fibrinogen is an accurate marker of disease activity in patients with polymyalgia rheumatica.

OBJECTIVE: The overall aim of this study was to establish whether plasma fibrinogen was a superior biomarker of disease activity in active PMR than the standard biomarkers, ESR and CRP. METHODS: Sixty patients with PMR were divided into active (n = 25) or inactive (n = 35) disease groups based on symptoms, physician assessment and biomarkers ESR and CRP. Plasma fibrinogen was assayed. Groups underwent assessment at baseline and 6 weeks. Disease activity as per the PMR activity score (PMR-AS) was recorded at all visits. Receiver operator curves (ROCs), predictive values and likelihood ratios were calculated for all biomarkers. RESULTS: Disease activity measures improved significantly in the active group between weeks 1 and 6 (P < 0.001). There was no significant difference between the activity scores at week 6 in the active group and the inactive group. Mean fibrinogen decreased from 5.2 to 3.5 g/l (normal <4 g/l) between weeks 1 and 6 in the active group. Mean ESR and CRP decreased from 59.6 to 24.3 mm/h (normal <30 mm/h) and 45.9 to 12.66 mg/l (normal <5 mg/l), respectively. Receiver operator curve analysis revealed fibrinogen to be more specific than either ESR or CRP for the detection of response to treatment in active PMR, with an overall sensitivity and specificity of 92% and 96%, respectively. Values above the upper limit of normal for fibrinogen, CRP and ESR were associated with likelihood ratios for active disease of 20.53, 2.9 and 2.8, respectively (P < 0.001). CONCLUSION: Plasma fibrinogen is at least as useful as CRP and ESR for the diagnosis of active PMR and more specific for confirmation of response to treatment than either ESR or CRP.

Basic calcium phosphate crystal-induced prostaglandin E2 production in human fibroblasts: role of cyclooxygenase 1, cyclooxygenase 2, and interleukin-1beta.

OBJECTIVE: To elucidate the mechanism of basic calcium phosphate (BCP) crystal-induced prostaglandin E(2) (PGE(2)) production in human foreskin fibroblasts (HFFs), to identify the signaling pathway involved in the induction of cyclooxygenase 2 (COX-2) messenger RNA (mRNA) by BCP crystals, to examine the effect of BCP crystals on interleukin-1beta (IL-1beta) mRNA expression, and to investigate the potential of phosphocitrate to abrogate the BCP crystal-induced effects. METHODS: PGE(2) levels were quantified using a commercial enzyme immunoassay kit. COX-2 and COX-1 transcript levels were quantified using real-time reverse transcriptase-polymerase chain reaction (RT-PCR). Induction of IL-1beta and COX-2 mRNA was examined by end-point RT-PCR. COX-2 protein expression was assessed by Western blotting. RESULTS: PGE(2) production measured 4 and 30 hours after BCP crystal treatment was higher in BCP crystal-treated (mean +/- SEM 1,891 +/- 273 pg/microg and 1,792 +/- 233 pg/microg, respectively) than in untreated (88 +/- 5 pg/microg and 205 +/- 93 pg/microg, respectively) HFFs. The PGE(2) produced after 4 hours was sensitive to inhibition with NS398, a selective COX-2 inhibitor, implying that it was COX-2 mediated, whereas the PGE(2) produced at 30 hours could not be completely inhibited by NS398. Real-time RT-PCR demonstrated a 23-fold increase in COX-2 mRNA that was maximal at 4 hours, whereas analysis of mRNA for COX-1 showed up-regulation of transcript peaking at 24 hours poststimulation (1.75-fold increase). The protein kinase C and phosphatidylinositol 3-kinase signal-transduction inhibitors bisindolylmaleimide I and LY294002, respectively, blocked BCP crystal-induced COX-2 mRNA in HFFs. In addition, BCP crystals were found to up-regulate the proinflammatory cytokine IL-1beta (maximal at 8 hours). The induction of both COX-2 and IL-1beta by BCP crystals was attenuated when the cells were treated with phosphocitrate. CONCLUSION: These findings indicate that BCP crystals may be an important amplifier of PGE(2) production through induction of the COX enzymes and the proinflammatory cytokine IL-1beta.

Whole-body MR imaging in the diagnosis of polymyositis.

OBJECTIVE: Our purpose was to evaluate the use of whole-body MR imaging in the assessment of the extent and distribution of muscle inflammation in patients with polymyositis. CONCLUSION: Whole-body turbo short tau inversion recovery imaging is a convenient complete method of evaluating patients with muscle inflammation caused by polymyositis. This imaging technique allows us to evaluate the total inflammatory burden by revealing multiple muscle groups not seen with standard protocols.

Hereditary hemochromatosis: a common, often unrecognized, genetic disease.

Hereditary hemochromatosis in people of northern European descent is more common than many physicians realize. It causes excessive gastrointestinal absorption of iron, leading to potentially fatal iron deposition in multiple organs. Early diagnosis and phlebotomy to reduce iron stores can prevent complications and provide normal life expectancy. Genetic testing of relatives of patients with hemochromatosis is warranted in some circumstances.