Are inflammation parameters true signs of activity? A contribution to the problem of process activity and progression in chronic polyarthritis

Among all laboratory parameters used today in the assessment of activity and progression of rheumatoid arthritis erythrocyte sedimentation rate (ESR) can only be recommended reservedly. ESR is influenced by anemia, reduction of plasma fibrinogen, dysproteinemia and by the concentration of acute phase proteins. Quantification of acute phase proteins especially of the C-reactive protein (CRP) correlates best with activity and progression of early forms of rheumatoid arthritis as well as with malignant courses. During the administration of alkylating agents - rise of ESR in spite of clinical improvement and decrease of CRP - and during antimalarials - clinical improvement, decrease of CRP and constant, unchanged ESR - the quantification of CRP turns out to be superior to ESR.     

The L1 protein as a new indicator of inflammatory activity in patients with juvenile rheumatoid arthritis

L1 is a major granulocyte and monocyte protein with Mr 36.5 kDa. It is released during leukocyte activation and detected in plasma by use of an enzyme immunoassay. In our study, L1, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), orosomucoid and haptoglobin were analyzed in 127 patients with juvenile rheumatoid arthritis (79 pauci, 33 poly and 15 systemic). L1, ESR and the acute phase proteins were all found to have positive correlations with the clinical joint assessments, with L1 having the strongest correlations. High correlation coefficients were found between L1 and orosomucoid (r = 0.83), ESR (r = 0.72), haptoglobin (r = 0.71) and CRP (r = 0.65), with p less than 0.001 for all the correlations.     

The clinical and prognostic significance of erythrocyte sedimentation rate (ESR), serum interleukin-6 (IL-6) and acute phase protein levels in multiple myeloma

Interleukin-6 (IL-6) and acute phase proteins are commonly increased in patients with multiple myeloma. Several of these acute phase proteins are believed to predict prognosis and influence survival. We measured interleukin-6 (IL-6), C-reactive protein (CRP), alpha-1-antitrypsin (a1AT), acid alpha-1-glycoprotein (a1AG), haptoglobin (HAP), transferrin (TRF), hemoglobin (Hb), beta-2-microglobulin (beta2M) and erythrocyte sedimentation rate (ESR) in 42 newly diagnosed multiple myeloma patients and 25 normal controls. At the time of blood collection, nine patients were at stage I of disease, 14 at stage II, and 19 at stage III according to the Durie and Salmon myeloma staging system. Mean +/- SD values of IL-6, CRP, a1AT, a1AG, HAP, beta2M, and ESR were significantly higher and Hb significantly lower than those found in the controls. Univariate analysis, using the log-rank test, showed that among the acute phase proteins, serum CRP (P < 0.002), a1AT (P < 0.008) and ESR (P < 0.008) were significantly correlated with survival. However, when a multivariate Cox proportional hazard model was performed, ESR, CRP, a1AT, a1AG and beta2M were identified as independent prognostic factors, while the others were not. We conclude that ESR, a simple and easily performed marker, was found to be an independent prognostic factor for survival in patients with multiple myeloma.     

Equivalence of the acute phase reactants C-reactive protein, plasma viscosity, and Westergren erythrocyte sedimentation rate when used to calculate American College of Rheumatology 20% improvement criteria or the Disease Activity Score in patients with early rheumatoid arthritis. Western Consortium of Practicing Rheumatologists.

OBJECTIVE: In an additive cohort of patients with early rheumatoid arthritis (RA), to determine the effect of substituting one acute phase reactant for another on the number of patients satisfying the American College of Rheumatology (ACR) 20% preliminary criteria for improvement, and on calculated Disease Activity Scores (DAS). METHODS: A total of 251 patients with 6.4 months average disease duration had detailed clinical assessments at entry and 6, 12, and 24 months in a multicenter prospective longterm observational study. Matched erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), and plasma viscosity (PV) assays were done at 366 time points. Disease modifying antirheumatic drugs were not started until after the baseline evaluation. RESULTS: After 6, 12, and 24 months, 50%, 53%, and 57% of patients were responders, as defined by the ACR 20% improvement criteria. The difference in response rates when ESR, CRP, or PV was used as the acute phase reactant ranged from 0.4% at 12 months to 3% at 24 months. Percentile distributions of the 366 matched CRP, ESR, and PV values were used to prepare a nomogram that can be used to calculate the other acute phase reactant values if the value of one is known. When the nomogram was used to impute ESR values from observed PV or CRP values, average DAS scores calculated with the actual ESR values were not different from average DAS scores calculated from the imputed ESR values. CONCLUSION: ESR, CRP, and PV are equally useful in calculating ACR 20% response rates in patients with active early RA. A nomogram can be used to impute ESR values from CRP or PV values; use of the imputed ESR values is as accurate as use of the actual ESR values to calculate average DAS.     

Validity aspects of erythrocyte sedimentation rate and C-reactive protein in ankylosing spondylitis: a literature review

The preliminary core set for endpoints in disease controlling antirheumatic therapy includes acute phase reactants. The objective of this clinically oriented literature review was to examine and compare the validity of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in ankylosing spondylitis (AS) clinical trials. A MEDLINE search was performed covering the years 1967 through April 1998. AS studies were identified and selected if they included ESR and/or CRP and either presented data about their relation with disease activity or were designed as longitudinal clinical trials. Additional studies were identified by scrutinizing references cited in the retrieved studies. The selected studies were examined for truth (association with disease activity), discriminative power (sensitivity to change and discrimination between active and inactive treatment in longitudinal clinical trials), and feasibility (e.g., applicability and costs) of ESR and CRP in AS. We identified 12 articles on the association of ESR and/or CRP with disease activity and 13 longitudinal clinical trials reporting ESR and/or CRP data. Although the applied definitions or disease activity proved very inhomogenous, there was some evidence that both acute phase reactants are correlated with disease activity. In terms of discriminative capacity the available data are inconclusive. Relevant feasibility aspects are general availability, technically simple measurement, and an advantage in the cost of ESR and central laboratory facilities for CRP. Acute phase reactants do not comprehensively represent the disease process in AS. Their worth in AS clinical trials is limited. Based on the currently existing data neither measure is clearly superior in terms of validity. When selecting an acute phase reactant, feasibility aspects may be most relevant in choice of measure.     

Inflammation proteins in Horton's disease. Prospective study of 25 patients

In a study of 25 giant cell arteritis patients, whose diagnoses were made by temporal artery biopsy, the authors compared the evolution of the erythrocyte sedimentation rate (ESR) with those of the acute phase proteins (APP): fibrinogen (F), C reactive protein (CRP), orosomucoid (O), haptoglobin (H) and alpha 2-globulins (alpha 2-G), before, during and after corticotherapy; 165 laboratory analyses were made. Prior to treatment, ESR was increased in 96% of the patients, O and H in 100%, F and CRP in 96% and alpha 2-G in 92%. CRP showed the greatest mean increase (21x). Statistically significant positive correlations were found between ESR and alpha 2-G, F, CRP and O. No significant relationship was observed between APP and the occurrence of ophthalmological complications or the length of treatment. The CRP level returned to normal within the first week of steroid therapy for 76% of the patients, before ESR, F and O. During the withdrawal phase of corticotherapy, an ESR greater than 30 mm almost always corresponded to an inflammatory syndrome and an ESR of less than 15 mm to its absence (kappa coefficient = 0.64, p less than 0.001); however, an ESR between 15 and 30 mm did not enable us to draw a conclusion as to the absence or presence of such a syndrome. After terminating steroid therapy, the relationship between ESR and an inflammatory syndrome was weaker (kappa coefficient = 0.57, p less than 0.02).(ABSTRACT TRUNCATED AT 250 WORDS)     

The acute phase response in gout

We studied the acute phase response in gout. Oral temperature, white blood cell count and differential, platelet count, Westergren erythrocyte sedimentation rate (ESR), and serum levels of the acute phase reactants serum amyloid A protein (SAA) and C-reactive protein (CRP) were all elevated. The number of involved joints correlated with levels of ESR, SAA and CRP. CRP correlated with temperature, differential count, ESR and SAA. The acute phase response resolved rapidly with treatment.     

Evidence that C-reactive protein or IL-6 are not surrogates for all inflammatory cardiovascular risk factors in hemodialysis patients

BACKGROUND/AIMS: In otherwise healthy adults, high C-reactive protein (CRP) levels are associated with cardiovascular disease and have been linked to an inflammatory state. The presence of vascular disease is also associated with increased expression of adhesion molecules, including soluble intercellular adhesion molecule (sICAM), vascular endothelial growth factor (VEGF) and leukocyte-derived myeloperoxidase (MPO). These associations suggest potential mechanisms whereby inflammation may injure the vascular endothelium, but the recognition of how these mediators act in concert remain poorly characterized. That the prevalence of atherosclerosis and markers of inflammation are increased in renal failure patients suggests that inflammation causes accelerated vascular disease. METHODS: In hemodialysis patients, we examined the relationships between plasma CRP and sICAM, VEGF and MPO longitudinally. We determined whether episodes of a high CRP value were paralleled by simultaneous increases in mediators of inflammatory injury or molecules associated with endothelial cell adhesion or growth and whether CRP levels correlated with those of VEGF and MPO. RESULTS: Episodic increases in CRP were accompanied by higher levels of VEGF, sICAM and MPO. However, there was no correlation between serum CRP levels or other acute phase proteins and either MPO or VEGF, nor was there a constant temporal relationship between MPO and CRP. By contrast, MPO and VEGF levels were closely correlated with one another during episodes of inflammation (p = 0.0001), and CRP and interleukin-6 levels were also correlated. Increases in MPO tended to be restricted to patients with grafts or catheters, and not those with AV fistulas. CONCLUSIONS: These results suggest that high plasma levels of CRP or other acute phase proteins in cross-sectional studies should be interpreted cautiously when defining mechanisms underlying cardiovascular disease in the hemodialysis patient population. One, or more than one inflammatory repertoire may be activated, one involving hepatic acute phase proteins and the other neutrophil activation and each may contribute separately to outcomes. Better prognostic information may be obtained by measurement of more markers than CRP alone, such as MPO and VEGF.     

Thrombopoietin is not uniquely responsible for thrombocytosis in inflammatory disorders

A few studies in patients with reactive thrombocytosis identified levels of the hormone higher than expected, and suggested that TPO behaves as an acute-phase protein and was responsible for increased platelet count. At the opposite, other studies did not find any significant rise of the hormone in patients who similarly developed reactive thrombocytosis. To gain further information on this topic, we compared TPO levels and platelet counts in two series of patients hospitalized for acute illnesses: one with strong elevation of both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), and the other with normal values. Within the group of subjects with high ESR and CRP, 38 had normal platelet counts, while 15 had thrombocytosis. No thrombocytosis was observed in control patients. Patients with high acute phase indexes had significantly higher TPO levels and platelet counts than control patients. We identified significant positive correlations between ESR and CRP, and between TPO and CRP. Interestingly, no significant relationship between platelet counts and TPO levels was find. When we grouped patients with acute-phase reaction according to absence or presence of thrombocytosis, we found similar TPO values. Conversely, positive correlations between platelet count and IL-6 and between TPO and IL-6 have been identified. All together our results confirm that TPO acts as an acute phase protein but exclude the possibility that it is uniquely responsible for thrombocytosis of inflammatory disorders, which might recognize in IL-6 a credible candidate as a cooperating factor.     

Serum alpha 1 antichymotrypsin concentration as a marker of disease activity in rheumatoid arthritis.

Serum alpha 1 antichymotrypsin (alpha 1ACT), C reactive protein (CRP), orosomucoid, and erythrocyte sedimentation rate (ESR) were measured sequentially in 20 patients with rheumatoid arthritis (RA) treated with gold or penicillamine. Pain score, morning stiffness, grip strength, and articular index were measured and a Mallya score calculated. Based on a total of 148 sets of observations, significant correlations were found between alpha 1ACT and other variables (p less than 0.001 except morning stiffness at p less than 0.05). The actual correlation coefficients indicated a closer association with the other laboratory tests, CRP (0.62), orosomucoid (0.69), and ESR (0.61), than with clinical measurements: pain score (0.38), articular index (0.41), grip strength (-0.3), morning stiffness (0.19), and Mallya score (0.5). Sequential data on individual patients showed differing patterns of change in the variables indicating the importance of measuring more than one acute phase protein (APP), especially when CRP is inappropriately low. Serum alpha 1ACT concentration does reflect disease activity in RA. Its potential advantages are discussed.     

Clinical significance of interleukin-6 measurement in early rheumatoid arthritis: relation with laboratory and clinical variables and radiological progression in a three year prospective study.

OBJECTIVE--To evaluate the clinical significance of interleukin-6 (IL-6) measurements in relation to laboratory and clinical measures of disease activity and radiological progression in early rheumatoid arthritis (RA). METHODS--A prospective study was performed in 51 patients with early RA during the first three years of the disease, with monthly clinical and laboratory assessments and biannual radiographs of the hands and feet. IL-6 was measured by enzyme linked immunosorbent assay (ELISA). Cross sectional (n = 51) and longitudinal (n = 20) correlations between plasma IL-6 concentrations and values of C reactive protein (CRP), serum amyloid A protein (SAA), erythrocyte sedimentation rate (ESR), haemoglobin (Hb), platelets, and joint scores were calculated, and correlations made between time integrated values of IL-6, CRP and ESR, and radiological progression over three years (n = 20). RESULTS--Significant correlations were found between IL-6 and the acute phase response and platelets, but variable results were obtained for the correlation between IL-6 and Hb. In contrast to a significant correlation between time integrated values of CRP or ESR and radiological progression, time integrated values of IL-6 did not correlate with radiological progression over three years follow up. CONCLUSION--The course of disease activity and the radiological progression of joint damage are better reflected by CRP, SAA, and ESR values than by plasma IL-6 concentrations, particularly in stages of low disease activity.     

Serum amyloid A concentrations in giant-cell arteritis and polymyalgia rheumatica: a useful test in the management of the disease.

A prospective clinical study of 23 patients with giant-cell arteritis (GCA) and/or polymyalgia rheumatica (PMR) was undertaken in order to assess the behaviour of the non-specific markers of the disease activity, the erythrocyte sedimentation rate (ESR) and other acute phase markers, particularly the C-reactive protein (CPR) and serum amyloid A apolipoprotein (apo SAA) levels during induction of disease remission by prednisone therapy, and possible further recurrence of GCA and/or PMR. The apo SAA measurement is more sensitive than the CRP measurement in determining disease activity (97% and 61%, respectively). The specificity of apo SAA is greater than ESR in the determination of inactive disease (86% and 77%, respectively). In some cases with clinically active disease the ESR and CRP were normal, whereas the apo SAA was always elevated. We conclude that the apo SAA measurement in combination with clinical data and other laboratory parameters may be useful in the management of GCA and/or PMR.     

Relationship between erythrocyte sedimentation rate and serum C-reactive protein in rheumatoid arthritis.

Serum C-reactive protein (CRP) and the erythrocyte sedimentation rate (ESR) were compared in 241 patients with rheumatoid arthritis (RA). There was a positive linear correlation between the 2 measurements with a high degree of variability. Neither age nor duration of RA had a detectable influence. The relationship between CRP and ESR was, however, altered by treatment with gold, penicillamine, or high doses of prednisone. It is suggested that serum CRP is the more sensitive measurement, but that CRP and ESR do not have identical clinical significance.     

Comparative usefulness of erythrocyte sedimentation rate and C-reactive protein in assessing the severity of ulcerative colitis]

BACKGROUND/AIMS: Although erythrocyte sedimentation rate (ESR) is included as a laboratory parameter in Truelove and Witts' classification, C-reactive protein (CRP) is also used for severity assessment in ulcerative colitis (UC). Frequently, the discordance between ESR and CRP is observed in clinical practice. The aim of this study was to determine which parameter is more related with clinical activity in UC patients. METHODS: A total of 155 patients with UC were identified from January 2004 to March 2005. Their medical records were reviewed within these patients, a total of 541 assessments of disease activity were made. Correlation of clinical activity and laboratory tests were evaluated by Pearson's correlation coefficient. RESULTS: Pearson's correlation coefficients of ESR and CRP with clinical symptoms were 0.376 and 0.258, respectively. The correlation coefficient between ESR and CRP was 0.403 (p=0.000). A total of 131 (24.2%) assessments revealed discordance between ESR and CRP. When discordance occurred, the correlation coefficients with clinical symptoms were 0.338 for ESR (p=0.000) and 0.034 for CRP (p>0.01). Dividing discordant patients into high ESR/low CRP group and low ESR/high CRP group, the coefficients were 0.420 for ESR and 0.226 for CRP in high ESR/low CRP group, and 0.333 for ESR and 0.068 for CRP in low ESR/high CRP group. CONCLUSIONS: The correlation analysis indicates that ESR appears to be a more reliable laboratory parameter of disease activity than CRP in assessing the severity of UC. In particular, when the level of ESR and CRP is discordant, ESR is more useful in assessing the disease activity in UC patients.     

The clinical and prognostic significance of erythrocyte sedimentation rate (ESR), serum interleukin‐6 (IL‐6) and acute phase protein levels in multiple myeloma

Summary Interleukin‐6 (IL‐6) and acute phase proteins are commonly increased in patients with multiple myeloma. Several of these acute phase proteins are believed to predict prognosis and influence survival. We measured interleukin‐6 (IL‐6), C‐reactive protein (CRP), alpha‐1‐antitrypsin (a₁AT), acid alpha‐1‐glycoprotein (a₁AG), haptoglobin (HAP), transferrin (TRF), hemoglobin (Hb), beta‐2‐microglobulin (β₂M) and erythrocyte sedimentation rate (ESR) in 42 newly diagnosed multiple myeloma patients and 25 normal controls. At the time of blood collection, nine patients were at stage I of disease, 14 at stage II, and 19 at stage III according to the Durie and Salmon myeloma staging system. Mean ± SD values of IL‐6, CRP, a₁AT, a₁AG, HAP, β₂M, and ESR were significantly higher and Hb significantly lower than those found in the controls. Univariate analysis, using the log‐rank test, showed that among the acute phase proteins, serum CRP (P < 0.002), a₁AT (P < 0.008) and ESR (P < 0.008) were significantly correlated with survival. However, when a multivariate Cox proportional hazard model was performed, ESR, CRP, a₁AT, a₁AG and β₂M were identified as independent prognostic factors, while the others were not. We conclude that ESR, a simple and easily performed marker, was found to be an independent prognostic factor for survival in patients with multiple myeloma.     

Observations on the interleukin-6 and acute phase protein profiles in the disease course of patients with lupus erythematosus.

In vitro models have shown that interleukin-6 (IL-6) is the main dominator of the stimulation of the full spectrum of acute phase proteins. This study describes IL-6 levels in relation to levels of acute phase proteins in 15 systemic lupus erythematosus (SLE) patients, with special attention given to those patients with increased serum levels of IL-6. Three episodes with elevated levels of IL-6 were observed in a period shortly after a flare-up of SLE, in three of the 15 patients. In one of these three patients a clear increase in the C-reactive protein (CRP) level, preceded by an IL-6 increase, was observed. In the other two patients, CRP levels remained unchanged. It is speculated that, next to IL-6, another signal is operative or needed for the start of an acute phase reaction. However, influences of the disease itself or of the administered therapy cannot be excluded as the cause of the described discrepancy between IL-6 and acute phase protein profiles in these two SLE patients.     

Visualization of DAS28, SDAI,and CDAI: the magic carpets of rheumatoid arthritis

There has been continuous debate regarding the applicability of various composite measures for the assessment of disease activity in rheumatoid arthritis (RA). In order to further dissect this issue, we numerically and graphically modeled 28-joint disease activity scale (DAS28), simplified disease activity index (SDAI), and clinical disease activity index (CDAI) by three-dimensional (3D) plotting. We wished to graphically visualize the relative contribution of various elements in the three activity indices to each other. We calculated DAS28 (3 variables), SDAI, and CDAI by the standard equations. We plotted 3D “carpets” showing all combinations of the corresponding variables yielding to DAS28?=?5.1, DAS28?=?3.2, DAS28?=?2.6, SDAI?=?26, SDAI?=?11, and SDAI?=?3.3. We also plotted the 3D carpet for CDAI. In patients with high or moderate disease activity, erythrocyte sedimentation rate (ESR) or C-reactive protein (CRP) was not a major confounding factor when calculating DAS28 and SDAI, respectively. In contrast, ESR and CRP highly overshadowed changes in joint counts and global assessments in patients with low disease activity (LDA) or those in remission. No reliable assessment of LDA can be performed in cases where ESR >54 mm/h or CRP >20 mg/dl. Similarly, remission cannot be determined if ESR >19 mm/h or CRP >5 mg/dl. As CDAI does not include acute phase reactants, CDAI may be a useful tool even in states of remission or LDA. Our results suggest that acute phase reactants are indeed major confounding factors and should be omitted when assessing RA disease activity at least in special cases.     

C反应蛋白检测在慢性阻塞性肺疾病的临床意义及与肺功能相关性研究

目的 探讨COPD患者急性加重期与稳定期血清C反应蛋白(CRP)含量变化的临床价值,及其与肺功能的相关性.方法 选择AECOPD患者46例,比较其治疗前后CRP水平及白细胞总数(WBC)、中性粒细胞计数(N)、血沉(ESR)和肺功能FEV1％.结果 AECOPD患者CRP阳性率高于其他指标,治疗后明显下降,具有统计学差异(P＜0.01).治疗前后CRP与FEV1％均呈负相关,但无统计学意义(P＞0.05).结论 CRP可作为AECOPD的敏感指标,及治疗效果的评价指标.     

Factors associated with hospital admission in patients reaching the emergency department with COPD exacerbation

Background

We aimed to investigate the relation of platelet count (PLT) and plateletcrit (PCT), mean platelet volume (MPV) and platelet distribution width (PDW) with other acute phase reactants and radiological extent in pulmonary tuberculosis (PTB).

Methods

One hundred patients with PTB (Group 1), 50 patients with community-acquired pneumonia (Group 2) and 28 healthy control individuals (Group 3) were included in this analytic study.

Results

WBC (White Blood Cell), ESR (Eritrocyte Sedimentation Rate), CRP (C-Reactive Protein), PLT and PCT values were both in Group 1 and Group 2 than in Group 3. PDW values were significantly higher in Group 1 than Group 3. WBC, ESR and CRP values were lower, while PLT and PCT values were higher in the Group 1 compared to Group 2 (p??0.05). ESR, CRP, PLT and PCT values were found higher in radiological advanced stage (Stage 3) patients with PTB, while hemoglobin (Hb) was found lower (p?Conclusions This study indicates that reactive thrombocytosis and higher PCT and PDW develop frequently in PTB and there is a relation between thrombocytosis and acute phase reactants, that is the inflammatory response. In addition, tuberculosis with radiological advanced stage is seen more frequently in the patients with thrombocytosis and higher PCT, drawing attention to the possible role of platelets in the cell-based immune process of tuberculosis.     

Serum amyloid A in the assessment of early inflammatory arthritis

OBJECTIVE: Acute phase serum amyloid A (A-SAA) has been reported to be more sensitive than C-reactive protein (CRP) as a marker of disease activity. It may function in immune regulation and is linked to the development of secondary amyloidosis. We investigated the profile of A-SAA in early inflammatory arthritis and compared A-SAA with CRP and erythrocyte sedimentation rate (ESR) in relation to diagnosis and disease activity. METHODS: Using a sensitive and specific ELISA, A-SAA was measured in the serum of 140 patients with early arthritis (disease duration 2 weeks to 24 mo, mean 6 mo). CRP was determined using a standard ELISA; ESR and clinical disease activity variables were also recorded. RESULTS: Sixty-four patients had rheumatoid arthritis (RA), 19 psoriatic arthritis (PsA), 28 undifferentiated arthritis (UA), and 29 other forms of arthritis. A-SAA levels correlated with both CRP (r = 0.73, p = 0.0001) and ESR (r = 0.6, p = 0.0001). The magnitude of the A-SAA response was greater than either the CRP or ESR, and very high A-SAA levels were observed in disease as early as 2 weeks. Highest A-SAA concentrations occurred in RA (median 70.3 mg/l, maximum 1542) compared with the other groups (medians, PsA: 33 mg/l; UA: 12.3 mg/l; other arthritis: 11.2 mg/l), with values > 520 mg/l observed exclusively in RA. A-SAA, unlike CRP or ESR, could distinguish patients with a final diagnosis of RA from those who had persistent UA. In RA, A-SAA provided the strongest correlations with clinical measurements of disease activity. Clinical improvement was also best represented by A-SAA, while disease deterioration was associated with a significant increase in A-SAA values, but not CRP or ESR. CONCLUSION: Compared with ESR or CRP, A-SAA correlates best with markers of disease activity, and in patients with recent onset arthritis, very high levels of SAA occur exclusively in RA. As A-SAA is sensitive to change and accurately reflects alterations in disease status, it is the best marker available for the assessment of inflammatory joint disease.