CRPS diagnosis based on inflammation marker analysis (original) (raw)
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Local cytokine changes in complex regional pain syndrome type I (CRPS I) resolve after 6months
PAIN, 2013
There is evidence that inflammatory processes are involved in at least the early phase of complex regional pain syndrome (CRPS). We compared a panel of pro-and antiinflammatory cytokines in skin blister fluids and serum from patients with CRPS and patients with upper-limb pain of other origin (non-CRPS) in the early stage (< 1 year) and after 6 months of pain treatment. Blister fluid was collected from the affected and contralateral nonaffected side. We used a multiplex-10 bead array cytokine assay and Luminex technology to measure protein concentrations of the cytokines interleukin-1 receptor antagonist (IL-1RA), IL-2, IL-6, IL-8, IL-10, IL-12p40, and tumor necrosis factor-alpha (TNF-a) and the chemokines eotaxin, monocyte chemotactic protein-1 (MCP-1), and macrophage inflammatory protein-1b (MIP-1b). We found bilaterally increased proinflammatory TNF-a and MIP-1b and decreased antiinflammatory IL-1RA protein levels in CRPS patients compared to non-CRPS patients. Neither group showed side differences. After 6 months under analgesic treatment, protein levels of all measured cytokines in CRPS patients, except for IL-6, significantly changed bilaterally to the level of non-CRPS patients. These changes were not related to treatment outcome. In serum, only IL-8, TNF-a, eotaxin, MCP-1, and MIP-1b were detectable without intergroup differences. Blister fluid of CRPS patients showed a bilateral proinflammatory cytokine profile. This profile seems to be relevant only at the early stage of CRPS. Almost all measured cytokine levels were comparable to those of non-CRPS patients after 6 months of analgesic treatment and were not related to treatment outcome.
Jordan Medical Journal, 2013
Objective: The involvement of the peripheral nervous system is not uncommon in rheumatoid arthritis (RA); the most common disorders are multiple mononeuritis, sensor motor neuropathy, and entrapment neuropathy. Several auto-antibodies are associated with the disease, but of the most important are the anti-cyclic citrullinated peptide (anti-CCP) antibodies. However, little is known, about the role of high sensitive C-reactive protein (Hs-CRP) in relation to disease activity in RA. The objectives were to look for the frequency of peripheral nerves involvement in chronic rheumatoid arthritis patients and to investigate the correlations between clinical, hematological, serological, and neurophysiologic findings. Methods: This study involved 48 patients with rheumatoid arthritis and 30 apparently healthy subjects as controls. Neurophysiologic assessment was performed for each patient and control subjects and the ELISA method was used for the quantitative measurement of serum anti-CCP antibodies and Hs-CRP concentrations by using special kits. Results: The mean duration of the disease was 6.76±0.795 years, the mean DAS28 for RA patients was 5.22±0.131, and the mean HAQ score was 1.00±0.06. Thirty-three (68.8%) of 48 cases with RA exhibited an electrophysiological evidence of neuropathy(ies): 14 (29.2%) patients with carpal tunnel syndrome (CTS), 9 (18.8%) patients with polyneuropathy, while 5 (10.4%) patients showed mononeuritis multiplex. There were highly significant increases in the mean values of serum anti-CCP antibody concentration (22.61 ± 2.34 Vs 5.47 ± 0.42 U/ml, P<0.001), serum Hs-CRP concentration (10.05 ± 0.64 Vs 2.81 ± 0.22 mg/l, P<0.001), and ESR (41.85±2.7 Vs 11.73±1.3 mm/hr, P<0.001) in the RA group compared to the control group. In patients with RA, significant negative correlations were observed between anti-CCP antibody concentration and sural nerve velocity (r =-0.233, P < 0.05) while significant positive correlation was found between anti-CCP antibody concentration with sural latency (r=0.231, P<0.05). The serum Hs-CRP level significantly positively correlated with the Stanford disability index (r=0.324, P<0.05), number of tender joint (r=0.296, P<0.05), and ESR (r=0.436, p<0.01). Conclusions: The commonest neurophysiologic abnormalities were carpal tunnel syndrome (CTS), followed by polyneuropathy. Serum anti-CCP antibodies concentration, serum Hs-CRP concentration, and disability index (DI) are significantly correlated with neuropathy and occurrence of neuropathy depends on the activity and/ or severity of rheumatoid arthritis.
Changes in Plasma Cytokines and Their Soluble Receptors in Complex Regional Pain Syndrome
The Journal of Pain, 2012
Complex Regional Pain Syndrome (CRPS) is a chronic and often disabling pain disorder. There is evidence demonstrating that neurogenic inflammation and activation of the immune system play a significant role in the pathophysiology of CRPS. This study evaluated the plasma levels of cytokines, chemokines, and their soluble receptors in 148 subjects afflicted with CRPS and in 60 genderand age-matched healthy controls. Significant changes in plasma cytokines, chemokines, and their soluble receptors were found in subjects with CRPS as compared with healthy controls. For most analytes, these changes resulted from a distinct subset of the CRPS subjects. When the plasma data from the CRPS subjects was subjected to cluster analysis, it revealed 2 clusters within the CRPS population. The category identified as most important for cluster separation by the clustering algorithm was TNFa. Cluster 1 consisted of 64% of CRPS subjects and demonstrated analyte values similar to the healthy control individuals. Cluster 2 consisted of 36% of the CRPS subjects and demonstrated significantly elevated levels of most analytes and in addition, it showed that the increased plasma analyte levels in this cluster were correlated with disease duration and severity. Perspective: The identification of biomarkers that define disease subgroups can be of great value in the design of specific therapies and of great benefit to the design of clinical trials. It may also aid in advancing our understanding of the mechanisms involved in the pathophysiology of CRPS, which may lead to novel treatments for this very severe condition.
Annals of Pathology and Laboratory Medicine, 2019
Objective: Despite the wide availability of markers to diagnose the established disease of RA, there is lack of evidence for the suitability of any of these established biomarkers for diagnosing the disease at an early stage of its pathogenesis. Hs-CRP has the potential to be useful asa predictor of early inflammation in clinically suspected RA cases. Methods: 80 patients (40: anti-CCP positive; 40: anti-CCP negative) irrespective of their age and gender were enrolled. RF status and hs-CRP levels were determined in these patients. Correlation of hs-CRP levels with anti-CCP was done. Results: Mean anti-CCP levels among RF positive and negative cases were 410 U/ml and 62.4 U/ml respectively. Among both the groups of anti-CCP positive and negative patients, majority had hs-CRP levels between 50-60 mg/l. Hs-CRP levels were more than 6 mg/l in majority of the suspected arthritis cases irrespective of the anti-CCP or RF status. Mean hs-CRP levels were 50.8 and 43.6 mg/l among anti-CCP positive and negative cases respectively by unpaired t-test. There was no correlation between serum anti-CCP and hs-CRP levels among both anti-CCP negative and positive cases. Conclusions: Hs-CRP when used alone or in combination with other established markers, can aid in the early diagnosis, prediction of course of disease and assessment of response to treatment in RA cases.
Clinica Chimica Acta, 2012
Introduction: Rheumatoid arthritis (RA) is an inflammatory autoimmune disease characterized by chronic joint inflammation and extra-articular manifestations, eventually leading to permanent disability without early therapeutic interventions. Methods: The analytical and clinical performance of an electrochemiluminescent immunoassay (ECLIA) (Roche Diagnostics, Indianapolis, IN) were determined for cyclic citrullinated peptide antibodies (anti-CCP) in the diagnostic assessment of rheumatoid arthritis compared to a plate-based anti-CCP enzyme immunoassay (EIA) (Inova Diagnostics, Inc.). Results: Imprecision studies on the automated Roche ECLIA demonstrated intra-assay CV's of b 3% and interassay CV's of b7%. The Inova EIA had intra-assay CV's of b 15% and inter-assay CV's of b 12%. The limit of quantitation of both assays was acceptable, and both assays showed similar linearity within the manufacturer's defined reportable ranges. Overall, analytical concordance was 62%, with 95.2% positive and 53.2% negative concordance. The clinical specificity in a normal population (n = 91) was 98.9% and 100% for Roche ECLIA and Inova EIA, respectively. The clinical specificity in a connective tissue disease population (n = 98) was 91.9% (95%CI, 86.0 to 96.5%) and 88.8% (95% CI, 81.0 to 93.6%) for Roche ECLIA and Inova EIA, respectively. Conclusion: The Roche ECLIA demonstrated similar analytical performance, although with improved intraassay precision, in comparison to the Inova EIA. The two methods also demonstrated similar clinical sensitivity and specificity. The Roche automated immunoassay is a viable alternative to the plate-based EIAs with the advantage of being performed on an automated platform.
Regulatory Peptides, 2003
In the present study, we have investigated the in vitro effect of calcitonin-related peptide (CGRP), neuropeptide Y (NPY), substance P (SP) and vasoactive intestinal peptide (VIP) at concentrations of 10−8, 10−9 and 10−10 M on the production of different proinflammatory cytokines or chemokines such as IL-1β, IL-6 and TNFα by peripheral whole blood cells from patients with rheumatoid arthritis, as well as from osteoarthritis patients studied as a control group without immunoinflammatory background. We have found that CGRP, NPY, SP and VIP stimulated significantly the production of those cytokines and chemokines in rheumatoid arthritis patients. In general, the stimulation was higher at the 10−9 M concentration, with SP and VIP, and in rheumatoid arthritis patients compared to osteoarthritis ones. Neuropeptides did not significantly modify the LPS-induced cytokine production by whole blood cells. The results indicate that physiological concentrations of the neuropeptides studied can modulate the inflammatory and immunological response, stimulating significantly the production of inflammatory cytokines by human whole blood cells in rheumatoid arthritis patients, as well as, in a minor way, in osteoarthritis patients.
Comparative study of anti-CCP and RF for the diagnosis of rheumatoid arthritis
APLAR Journal of Rheumatology, 2007
Aim: To determine the frequency of anti-cyclic citrullinated peptide antibody (anti-CCP) in a group of patients with rheumatoid arthritis and another group with other rheumatic diseases. Patients and methods: Anti-CCP1 and rheumatoid factor (RF) titres were determined in 320 serum samples; 136 from RA patients, 184 from control patients (165 patients with rheumatic diseases other than RA, and 21 patients with lymphoproliferative diseases). Results: The sensitivity of Anti-CCP was 62.5% (95% CI: 53-70%) for the diagnosis of RA with a specificity of 89.1% (95% CI: 83-93%). The sensitivity of RF was 85.3% (95% CI: 79-91%). The specificity was 64.7% (95% CI: 57-71%). Conclusions: Anti-CCP1 has not very high specificity for RA regarding other rheumatic disease. However it is still very helpful for the diagnosis of RA.