Relationship between some acute phase reactants and the Bath Ankylosing Spondylitis Disease Activity Index in patients with Ankylosing Spondylitis.

Objectives: The aims of this study were to investigate a possible relationship between the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and some acute phase reactant (APR) levels in patients with ankylosing spondylitis (AS).

Methods: Twenty outpatients who fulfilled the modified New York criteria for AS were included in the study. Laboratory activity was assessed by examining erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), haptoglobin (Hp), and [[beta].sub.2] microglobulin ([[beta].sub.2]MG). Disease activity was assessed according to the BASDAI, which includes a 10-point visual analogue scale to measure pain, fatigue, morning stiffness, swelling, and areas of local tenderness.

Results: When APR values were analyzed for the BASDAI, a positive correlation between CRP and BASDAI was observed (r = 0.556, P < 0.05). There was no clear, statistically significant correlation between BASDAI and the other APRs (ESR, r = 0.328, P > 0.05; Hp, r = 0.035, P > 0.05; and [[beta].sub.2]MG, r = -0.190, P > 0.05).

Conclusions: Our data suggest that CRP is a better marker of disease activity than ESR, Hp, and [[beta].sub.2]MG.

Key Words: acute phase reactants, ankylosing spondylitis, disease activity index

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Ankylosing spondylitis (AS) is an inflammatory disease of unknown origin that first affects the spine and adjacent structures and commonly progresses to eventual fusion (ie, ankylosis) of the involved joints. (1) It affects primarily the spine and hip joints and causes progressive bone fusion, including the costovertebral joints, as well as erosion and destruction of the vertebral endplates, osteophytes, subchondral sclerosis, ossification of the intervertebral disc, narrowing of the joint space, and osteoporosis. (2-4) AS is characterized by mild or moderate flare-ups of active spondylitis alternating with periods of quiescence.

The acute phase response to tissue injury and inflammation is accompanied by a dramatic increase in the hepatic synthesis of plasma proteins known as acute phase reactants (APRs). The APRs can be useful in assessing the degree of inflammation. (5,6) The most important APRs are C-reactive protein (CRP), serum amyloid A, haptoglobin (Hp), and [[beta].sub.2] microglobulin ([[beta].sub.2]MG).

Human [[beta].sub.2]MG is an 11.8-kDa protein identical to the light chain of the human leukocyte antigen (HLA)-A, HLA-B, and HLA-C. [[beta].sub.2]MG is expressed on nucleated cells, is found at low levels in the serum and urine of healthy individuals, and is increased in inflammatory diseases, some viral diseases, renal dysfunction, and autoimmune diseases. (7,8)

Hp is an acute phase protein used in the detection of in vivo hemolysis and inflammation. The primary function of Hp is the irreversible binding of free oxyhemoglobin in plasma. This complex is then removed within minutes by the reticuloendothelial system. Elevated values are present in chronic and acute inflammatory and neoplastic diseases. (9)

The erythrocyte sedimentation rate (ESR) is an index of the acute phase response that reflects mainly the concentrations of fibrinogen and [alpha]-globulins. It is commonly used to assess the acute phase response. The CRP, however, may complement the ESR in monitoring chronic inflammation in, for example, rheumatic diseases.

The Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) is used to evaluate disease activity. It was developed as a composite index consisting of an evaluation on a 10-point Visual Analogue Scale of fatigue, axial pain, peripheral pain, morning stiffness, discomfort, and enthesopathy. (10) The aim of this study was to investigate the BASDAI and certain APR levels in patients with AS.

Materials and Methods

Twenty consecutive outpatients who fulfilled the modified New York criteria for AS and 20 healthy hospital staff with no history of inflammatory disease were included in the study. Eighteen patients had HLA-B27. The clinical assessment included demographic data regarding age, sex, weight, and duration of disease. There were 16 men and 4 women. The patients' mean age was 43.6 [+ or -] 7.1 (range, 33-60 yr). The mean disease duration was 10.4 [+ or -] 3.7 years (range, 4-18 yr). Among the controls (n = 20), there were 15 men and 5 women whose mean age was 42.4 [+ or -] 8.4 years (range, 27-55 yr).

Disease activity was assessed with the BASDAI. (10) The BASDAI consists of six questions relating to the five major symptoms of AS. Each individual was scored from 0 to 10 according to the Visual Analogue Scale. Morning stiffness was measured on a 0- to 2-hour time scale (marked at every 15-min interval) and then converted to a 0 to 10 scale to obtain the final BASDAI score. (10)

At the time of sampling, 13 patients were undergoing a regimen of combined nonsteroidal anti-inflammatory drugs and sulfasalazine, and 7 patients were on a regimen of only nonsteroidal anti-inflammatory drugs. The patients were allowed to continue their previous drug regimens.

We excluded patients who had evidence of severe renal, hepatic, endocrine (ie, Paget's disease, hyperthyroidism, hyperparathyroidism), hematologic, lymphoproliferative, and other malignant diseases. In this study, only patients with AS without an associated condition were assessed. The exclusion criteria for the control group were the same as those for the AS group.

ESR was determined according to the Westergren method, and CRP was measured according to a nephelometric method (Beckman Array Protein System; Beckman Coulter, Inc., Fullerton, CA). Serum [[beta].sub.2]MG and Hp levels were determined with a commercially available kit by nephelometric method (Beckman Coulter Image; Beckman Coulter, Inc.).

Data were processed using SPSS software (SPSS, Inc., Chicago, IL). Laboratory results were calculated as mean [+ or -] standard deviation. Differences between groups were analyzed with the Mann-Whitney U test. Spearman's rank-correlation coefficient was used to assess the correlation between variables. P < 0.05 was regarded as significant.

Results

Demographic data of the 20 patients with AS and 20 healthy volunteers included in the study are shown in Table 1. There were no statistically significant differences between the two groups with respect to demographic data such as age, sex, and weight (P > 0.05). Laboratory findings of patients with AS and healthy controls are shown in Table 2. The serum ESR, CRP, and Hp levels in patients with AS were significantly higher than those in healthy controls (P < 0.01, P < 0.001, and P < 0.01, respectively). Although the serum levels of [[beta].sub.2]MG in patients with AS were higher than those in the control group, the differences were not statistically significant (P > 0.05). The BASDAI scores of patients with AS are shown in Table 2. A positive correlation between BASDAI and CRP was observed (r = 0.556, P < 0.05) (Fig. 1). There were no clear, statistically significant correlations between BASDAI and other APRs such as ESR, Hp, and [[beta].sub.2]MG (r = 0.328, P > 0.05; r = 0.035, P > 0.05; and r = -0.190, P > 0.05, respectively).

[FIGURE 1 OMITTED]

Discussion

Inflammatory tissue injury induces changes in the concentrations of several plasma proteins' APRs. (11) We conducted this research to determine the correlation between some APRs (ESR, CRP, Hp, and [[beta].sub.2]MG) and the BASDAI, an index designed to evaluate clinical disease activity.

In this study, we detected a significant correlation only between CRP and BASDAI in the patients with AS. Although several researchers have reported that CRP would be suitable, (12-14) others have reported that the use of CRP in patients with AS is limited. (15,16) CRP blood levels are not directly affected by the commonly used anti-inflammatory drugs, including steroids; therefore, any change in CRP reflects a change in activity of the underlying disease. (17,18) Our data suggest that, of the markers we examined, CRP is the best marker of disease activity. Although elevated CRP level is not specific for any condition, it is an index of ongoing inflammation and thus provides a valuable adjunct to the clinical assessment. (19)

Although the ESR levels of patients with AS were higher than those in healthy volunteers, we did not find a significant correlation between ESR and BASDAI. Several factors affect ESR, including age, sex, anemia, infections, and pregnancy; therefore, the use of this marker is limited. (20,21) Furthermore, normal ESR has been noted in patients with clinically active AS, as well as in the presence of elevated levels of serum CRP and other markers. Elevated ESR is present in patients with AS, and therefore it may not correlate with disease activity. The CRP level increases quickly after an inflammatory event and returns to normal within 1 week, whereas the ESR level increases slowly in response to increased production of fibrinogen by the liver and decreases slowly once the activity has subsided. CRP levels offer better insight than ESR into the progress of inflammation because of its more rapid kinetics. (11) CRP therefore may be a better marker. (22)

In our study, we could not detect a significant correlation between [[beta].sub.2]MG and Hp blood levels and BASDAI. Although blood levels were higher in patients with AS than in healthy volunteers, [[beta].sub.2]MG can serve as a nonspecific but relatively sensitive marker of various neoplastic, inflammatory, and infectious conditions. (7,8) Serum Hp levels are increased greatly when there is extensive tissue damage (ie, inflammation) or necrosis. Hp may exhibit immunosuppressive activities. (9,23) Our results suggest that in patients with AS, CRP is a better index of disease activity than ESR, [[beta].sub.2]MG, and Hp.

Table 1. Demographic characteristics of patients with AS and healthy
controls (a)

Characteristic            AS group           Controls           P value

No. of patients (M/F)     20 (16/4)          20 (15/5)             NS
Mean age (yr)             43.6 [+ or -] 7.1  42.4 [+ or -] 8.4     NS
Mean weight (kg)          67.1 [+ or -] 7.5  68.2 [+ or -] 8.7     NS
Mean duration of disease  10.4 [+ or -] 3.7  --                    NS
  (yr)

(a) AS, ankylosing spondylitis; NS, not significant; --, no data.

Table 2. Serum levels of some acute phase reactants of patients with AS
and healthy controls, with BASDAI scores in patients with AS (a)

Parameter         AS group              Controls             P value

ESR (mm/h)         34.9 [+ or -] 25.1   17.0 [+ or -] 12.3    <0.01
CRP (mg/L)          2.24 [+ or -] 2.0    0.36 [+ or -] 0.25   <0.001
[beta][.sub.2]MG    0.21 [+ or -] 0.15   0.13 [+ or -] 0.02   >0.05
  (mg/dl)
Hp (mg/dl)        127.2 [+ or -] 39.0   73.2 [+ or -] 25.5    <0.01
BASDAI score        4.32 [+ or -] 1.50  --

(a) AS, ankylosing spondylitis; ESR, erythrocyte sedimentation rate;
CRP, Creactive protein; [[beta].sub.2] MG, [[beta].sub.2] microglobulin;
Hp, haptoglobin; BASDAI, Bath Ankylosing Spondylitis Disease Activity
Index.

Accepted December 6, 2002.

Copyright [c] 2004 by The Southern Medical Association

0038-4348/04/9704-0350

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RELATED ARTICLE: Key Points

* Ankylosing spondylitis is characterized by mild or moderate inflammation flares of active spondylitis alternating with periods of nearly total or total quiescence.

* The Bath Ankylosing Spondylitis Disease Activity Index is used to evaluate clinical disease activity.

* Some acute phase reactants (erythrocyte sedimentation rate, C-reactive protein, [[beta].sub.2] microglobulin, and haptoglobin) are useful for assessing the inflammatory response and disease activity.

* Among the markers tested, C-reactive protein was found to be the best marker of disease activity index (the Bath Ankylosing Spondylitis Disease Activity Index).

Kadir Yildirim, MD, Akin Erdal, MD, Saliha Karatay, MD, Meltem Alkan Melikoglu, MD, Mahir Ugur, MD, and Kazim Senel, MD

From the Department of Physical Medicine and Rehabilitation, School of Medicine, Ataturk University, Erzurum, Turkey.

Reprint requests to Kadir Yildirim, MD, Ataturk Universitesi Tip Fakultesi Fiziksel Tip ve Rehabilitasyon Anabilim Dah, 25240 Erzurum, Turkey. Email: [e-mail]