Active Sacroiliitis on MRI, Inflammation Biomarkers, and Clinical Disease Activity: What Relationship Does Link Between the Three, in Non-Radiographic Axial Spondyloarthritis?

Magnetic resonance imaging of sacroiliac joints (MRI SI) is the gold standard imaging tool for axial spondyloarthritis (ax SpA) diagnosis, when the pelvic radiograph is normal or non-conclusive. In fact, subchondral bone marrow edema (BME) is the primary MRI feature of early ax SpA. The associated factors with active sacroiliitis on MRI are still not properly elucidate. The main objective of this study is to identify the relationship between active sacroiliitis on MRI, biomarkers of inflammation and Disease Activity Scores. Materials and methods: Our work could be categorized as a cross sectional study that enrolls all patients with nonradiographic axial spondyloarthritis (nr axSpA), meeting each; the assessment of SpondyloArthritis international Society axSpA criteria (ASAS 2009), and who were admitted in our Rheumatology Department, in the university hospital Hassan II of Fez (Morocco), all along the period laying between January 2012 and March 2018. The relationship between MRI-SI, Ankylosing Spondylitis Disease Activity Score (ASDAS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), C reactive protein and erythrocyte sedimentation rate was investigated. Results: 105 patients were involved in the study. The average age was [44years ± 13.5]. The Sex ratio was about [1.4]. 29 % of patients were smokers. 76% of cases had active sacroiliitis on MRI, while only 28% had inactive sacroiliitis. The average CRP serum level was roughly [23.5 ± 36mg / l]. On the other side, the ESR blood level was almost [25.9±24mm/h]. 94.2% of patients used non-steroidal antiinflammatory drugs (NSAIDs). The average ASDAS value was about [2.3 ± 1]. Whereas the BASDAI one was [4.2± 1], and the BASFI one was about [4± 1.5]. Actually, No significant relationship was found between active sacroiliitis and inflammation’s biomarkers. Indeed, men had 5.6 times more active sacroiliitis, of which smokers had even 3 times more the risk to develop active sacroiliitis, while treatment with NSAIDs was proved to be a protective factor. Conclusion: Biomarkers of inflammation cannot be used as a marker of objective inflammation of sacroiliac joints on MRI; hence, the necessity of MRI screening, and more additional studies with larger number of patients, should be conducted, to identify this association even better. KEYSWORDS: Axial Spondyloarthritis, Biomarkers of Inflammation, Active Sacroiliitis, MRI of Sacroiliac Joints. Correspondence : Noura Naji, Rheumatology department, Hassan II University Medical Center, Fez, Morocco. Adresse e-mail : najinouira@gmail.com Copyright © 2020 Noura Naji et al. This is an open access article distributed under the Creative Commons Attribution 4.0 International, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. Naji N et al. Non-Radiographic Axial Spondyloarthritis Integr J Med Sci.2020;7:4p 2 INTRODUCTION Spondylarthritis might be defined as a group of chronic inflammatory rheumatic diseases, characterized by a predominant damage of the spine and sacroiliac joints. Enthesitis is also a common feature, with a tendency to enthesophytes formation. It is actually the second most frequent chronic inflammatory rheumatic disease after rheumatoid arthritis. The diagnostic value of sacroiliac joints MRI (MRI-SI) in non-radiographic axial spondyloarthritis (nr axSpA) is nowadays clearly established [1]. The contribution of MRI to our understanding of spondyloarthritis including ankylosing spondylitis (AS) is indisputable. In fact, MRI can be used to detect inflammatory lesions of the spine and sacroiliac joints. Furthermore, spinal MRI is currently considered as being a powerful tool to bring out the treatment efficacy by detecting improvement, persistence or new onset of spinal inflammation in AS [2]. The associated factors with active sacroiliitis are yet poorly understood. This study aims to investigate the relationship existing between active sacroiliitis, CRP blood level, and clinical activity scores of nonradiographic axial spondyloarthritis. MATERIALS AND METHODS : The concerned population: It is a question of a cross sectional study, that enrolls the whole patients with axial spondyloarthritis admitted in the Rheumatology Department of University hospital Hassan II of Fez, in Morocco , throughout the period laying between January 2012 and March 2018. All the Patients who met the Assessment of SpondyloArthritis international Society (ASAS) criteria for axSpA, were involved [3]. The data collected from each patient’s register, are the following: • Age, gender, address, education level, career, and tobacco consumption. • Clinical disease activity measures: The disease activity was assessed by the mean of ankylosing Spondylitis disease Activity Score with C reactive protein (ASDAS-CRP), and Bath Ankylosing Spondylitis Disease Activity Index (BASDAI). The disease was considered active when BASDAI ≥4 and ASDAS ≥2,1. • Biological markers: Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP). CRP was considered to be negative when it is less than 6 mg/l, and positive if it is over >6 mg/l. • The functional effect of axSpA was evaluated by mean of BASFI: Bath Ankylosing Spondylitis Functional Index in a validated Moroccan version [4]. • The use or not of NSAIDs. MRI of sacroiliac joints: Definition of active sacroiliitis on MRI: The ASAS group concluded that the presence of inflammation (defined as Bone Marrow Oedema – BMO) is the principal observation required by the current definition and no additional findings are necessary. The description for sacroiliac joint BMO consistent with active SpA is : 1. Bone marrow oedema (BMO) on a T2-weighted sequence sensitive free water (such as short tau inversion recovery (STIR) or T2FS) or bone marrow contrast enhancement on a T1-weighted sequence (such as T1FS post-Gd). 2. Inflammation must be clearly present and located in a typical anatomical area (subchondral bone). 3. MRI appearance must be highly suggestive of SpA. [5] Statistical analysis : Statistical analysis was performed using the EPI INFO software 3.5.4 version. Statistical comparison was carried out between patients who do have an active sacroiliitis and the ones who do not. A multivariate logistic regression analysis was performed to calculate the odds ratio (OR) of various clinical parameters. P value was considered significant if it was less than 0.05. Results : 105 patients were included in our study. The average age of patients was 44 years+/13.5 [15, 80] with a sex ratio Female/Male of 1.4 (62 women and 43 men). MRI of sacroiliac joint’s showed that 76% of patients had active sacroiliitis (figure 1) whereas 28% of them had inactive sacroiliitis (figure 2). Moreover, 29% of cases were smokers, and 94.2% took NSAIDs. Figure 1 : Active sacroiliitis Picture 2 : Inactive sacroiliitis As far as biomarkers are concerned; the average blood level of ESR was 25.9 mm H1± 24 and the one of CRP was 23.5 mg/l ± 36. Regarding the axSpA activity and functional effect, the mean value of BASDAI, ASDAS and BASFI were 4.2 ± 1 [1,8], 2.3 ± 1 [1, 5] and 4 ± 1.5 [0.5, 7] respectively. The univariate analysis figures in Table1, the associated factors with active sacroiliitis were male gender, tobacco consumption, BASDAI, BASFI and use of NSAIDs. 86.9% of women and 53,5% of men had active sacroiliitis, while13.1% of women and 46.5% of men had inactive sacroiliitis (p=0,01).48.3% of the smokers had active sacroiliitis, whereas 51.7% had inactive sacroiliitis (P=0,03). BASDAI and BASFI were higher in case of active sacroiliitis, the p value was (p=0,01) and (p=0,000), respectively. Naji N et al. Non-Radiographic Axial Spondyloarthritis Integr J Med Sci.2020;7:4p 3 Concerning the use of NSAIDs, 75.5% of patients had active sacroiliitis while 24.5% of them had inactive sacroiliitis (p=0, 04). (Table 1) Table 1: Characteristics of patients with axial spondyloarthritis included in this study: bivariate analysis Total : N=104 ; Males N= 43 (41,3 %) ; Females N=61 (58,7 %) After multiple logistic regression analysis, the factors associated with active sacroiliitis were male gender, tobacco consumption and NSAIDs use. Men had almost 5.6 times more the risk of developing an active sacroiliitis [CI: 1.8-17.5], while smokers had 3 times more the risk of having an active sacroiliitis [CI: 1.00-8.7]. However, NSAIDs are considered as a protective factor against active sacroiliitis 0Ra= 0.16; [CI: 0.45-0.96]. (Table 2) Table 2: Characteristics of patients with axial spondyloarthritis included in this study: multivariate analysis Relationship between biomarkers of inflammation and active sacroiliitis on MRI: There was a significant correlation between BASDAI, BASFI and inflammation of sacroiliac joint’s on the MRI (p=0,01), (p=0,000),respectively. No other significant association was denoted, neither between inflammation biomarkers (CRP and ESR) and active sacroilitis on MRI, nor with disease activity assessed by ASDAS CRP measurement; (p=0,27), (p=0,69), (p=0,86), respectively. DISCUSSION This study shows that inflammation of SI joint’s on MRI, is not correlated to CRP serum levels. However, the literature reviews report inconsistent results. In fact, several studies proved an association between CRP blood level and the SI inflammation on the MRI, [6, 7, 8, 9, 10]. While many others [11, 12, 13, 14] didn’t bring out any similar association, as it is the case in our study. These contradictory findings may reflect differences between the studies in terms of the baseline status of their cohorts. In addition, a recent study showed that only CRP serum level is linked to MRI SI joints inflammation in patients with short disease duration versus patients with longstanding disease [15]. This observation indicates also that the relationship between inflammation of SI joints on MRI and biomarkers may change in the course of the disease. This may be a bia