Prevalence and predictors of atlanto-axial subluxation in rheumatoid arthritis after 12-years' follow-up (ESPOIR Cohort).

OBJECTIVES: Anterior atlanto-axial subluxation (AAS), defined as an anterior atlanto-dental interval ≥3 mm, can occur in RA and carries a risk of severe neurological impairments. Our objective was to determine the prevalence and predictors of radiographic aAAS after 12 years' follow-up of patients with early polyarthritis. METHODS: We studied patients enrolled in the early polyarthritis cohort ESPOIR (Study and Monitoring of Early Undifferentiated Arthritis) between 2002 and 2005 (at least two swollen joints for >6 weeks and <6 months, no other diagnosis than RA, and no previous exposure to glucocorticoids or DMARDs). All patients still in the cohort after 12 years had dynamic cervical-spine radiographs taken then read by two blinded observers. To evaluate how well combinations of tests performed at baseline and 10 years predicted aAAS after 12 years, univariate analysis and multiple logistic regression procedure were applied. RESULTS: Of 323 patients followed for 12 years, 15 (4.6%; 95% CI 2.8, 6.4) had aAAS. Among baseline variables, only IgA RFs were associated (P < 0.05) with aAAS (sensitivity 60%, specificity 75%). Among data collected after 10 years, oral CS therapy during the 10-year interval, treatment by DMARDs, CRP (mg/dl) and positive tests for RFs were associated with aAAS after 12 years, but only CRP and RFs remained in a model of logistic regression (combination predicted aAAS with a sensitivity of 60% for a specificity of 90%). CONCLUSION: In conclusion, the prevalence of aAAS after 12 years was 4.6% in the ESPOIR cohort, with no patients having severe aAAS. Although some factors were found to be statistically associated to AAS, the event is too rare to allow a clinical relevance.

Spinal-pelvic orientation: potential effect on the diagnosis of spondyloarthritis.

OBJECTIVE: To assess associations of spinal-pelvic orientation with clinical and imaging-study findings suggesting axial SpA (axSpA) in patients with recent-onset inflammatory back pain. METHODS: Spinal-pelvic orientation was assessed in DESIR cohort patients with recent-onset inflammatory back pain and suspected axSpA, by using lateral lumbar-spine radiographs to categorize sacral horizontal angle (<40° vs ⩾40°), lumbosacral angle (<15° vs ⩾15°) and lumbar lordosis (LL, <50° vs ⩾50°). Associations between these angle groups and variables collected at baseline and 2 years later were assessed using the χ2 test (or Fisher's exact) and the Mann-Whitney test. With Bonferroni's correction, P < 0.001 indicated significant differences. RESULTS: Of 362 patients, 358, 356 and 357 had available sacral horizontal angle, lumbosacral angle and LL values, respectively; means were 39.3°, 14.6° and 53.0°, respectively. The prevalence of sacroiliitis on both radiographs and MRI was higher in the LL < 50° group than in the LL ⩾50° group, but the difference was not statistically significant. Clinical presentation and confidence in a diagnosis of axSpA did not differ across angle groups. No significant differences were identified for degenerative changes according to sacral horizontal angle, lumbosacral angle or LL. CONCLUSION: Spinal-pelvic balance was not statistically associated with the clinical or imaging-study findings suggesting axSpA in patients with recent-onset inflammatory back pain.

Association of lumbosacral transitional vertebra and sacroiliitis in patients with inflammatory back pain suggesting axial spondyloarthritis.

OBJECTIVE: Lumbosacral transitional vertebras (LSTVs) are common in the general population, but their potential impact on the sacroiliac joints is unclear. We aimed to determine the prevalence of LSTVs and to assess their associations with sacroiliitis by standard radiography and MRI in a population with suspected axial spondyloarthritis. METHODS: The data were from the DESIR cohort of 688 patients aged 18-50 years with inflammatory low back pain for ⩾3 months but <3 years suggesting axial spondyloarthritis. The baseline pelvic radiographs were read by two blinded readers for the presence and type (Castellvi classification) of LSTVs. Associations between LSTVs and other variables collected at baseline and at the diagnosis were assessed using the χ2 test (or Fisher's exact test) or the Mann-Whitney test. RESULTS: LSTV was found in 200/688 (29.1%) patients. Castellvi type was Ia in 54 (7.8%), Ib in 76 (11.0%), IIa in 20 (2.9%), IIb in 12 (1.7%), IIIa in 7 (1.0%), IIIb in 21 (3.0%) and IV in 10 (1.4%) patients. Compared with the group without LSTVs, the group with LSTVs had higher proportions of patients meeting modified New York criteria for radiographic sacroiliitis (19% vs 27%, respectively; P = 0.013) and Assessment of SpondyloArthritis international Society MRI criteria for sacroiliitis (29% vs 39%, respectively; P = 0.019). CONCLUSION: In patients with inflammatory back pain suggesting axial spondyloarthritis, LSTVs are associated with both radiographic and MRI sacroiliitis.

Efficacy of first-line tocilizumab therapy in early polymyalgia rheumatica: a prospective longitudinal study.

BACKGROUND: Glucocorticoids are the cornerstone treatment of polymyalgia rheumatica (PMR) but induce adverse events. OBJECTIVES: To evaluate the efficacy and safety of first-line tocilizumab in PMR. METHODS: In a prospective open-label study (ClinicalTrials.gov: NCT01713842), 20 glucocorticoid-free patients fulfilling Chuang's PMR criteria, with symptom onset within the last 12 months and a PMR activity score (PMR-AS) >10, each received three tocilizumab infusions at 4-week intervals, without glucocorticoids, followed by oral prednisone from weeks 12 to 24 (0.15 mg/kg if PMR-AS ≤10 and 0.30 mg/kg otherwise). The primary end point was the proportion of patients with PMR-AS≤10 at week 12. RESULTS: Baseline median PMR-AS was 36.6 (IQR 30.4-43.8). At week 12, all patients had PMR-AS≤10 and received the low prednisone dosage. Median PMR-AS at weeks 12 and 24 was 4.5 (3.2-6.8) and 0.95 (IQR 0.4-2), respectively (p<0.001 vs baseline for both time points). No patient required rescue treatment. Positron emission tomography-CT showed significant improvements. The most common adverse events were transient neutropenia (n=3) and leucopenia (n=5); in one patient, the second tocilizumab infusion was omitted due to leucopenia. CONCLUSIONS: Tocilizumab monotherapy is effective in recent-onset PMR. Randomised controlled trials are warranted. TRIAL REGISTRATION NUMBER: NCT01713842.

A functional and bilateral ischiofemoral impingement with muscular hypertrophy in an 11-year-old dancer.

Ischiofemoral impingement syndrome (IFIS) is an unusual cause of hip pain. Certain strenuous sports can cause this impingement, such as dancing. We report the case of an 11-year-old ballet dancer with bilateral IFIS secondary to overtraining and hypertrophy of the quadratus femoris. This syndrome is frequently evoked in the field of orthopedics following hip replacement. Bilateral IFIS is rare and should be sought in the context of an intense sport such as dance when any other cause has been eliminated.

Reproducibility and diagnostic value of a new method using ratios to diagnose anterior atlanto-axial subluxation on plain radiographs.

OBJECTIVES: Measures on conventional radiography are used to detect, especially in rheumatoid arthritis, upper cervical spine instabilities (CSIs) with the anterior and posterior atlanto-dental intervals (AADI and PADI) measurements. Our objective was to evaluate the diagnostic performance and reliability of AADIs and PADIs extrapolated based on ratios in assessing anterior atlanto-axial subluxation (aAAS) when plain radiographs do not allow the measures. METHODS: Radiographies of 119 patients were randomly selected. Two blinded observers performed two measurements of the odontoid sagittal diameter (O), axis body base sagittal diameter (C2), AADI, PADI, Clark station and Ranawat index, and the AADI/O, AADI/C2, PADI/O and PADI/C2 ratios were calculated. The diagnostic value of AADI and PADI extrapolated from the AADI/O, AADI/C2, PADI/O and PADI/C2 ratios was evaluated using ROC curves, with AADI>2.9mm used as the gold standard. RESULTS: Among the 119 patients, 12 patients had aAAS (AADI>2.9mm), 6 of them had severe aAAS (AADI>8.9mm and/or a PADI<14mm), and 6 patients had vertical AAS (Clarks station=2 or 3 and/or Ranawat index<13mm). The AADI extrapolated from the AADI/O and AADI/C2 ratios has excellent intra- and inter-observer reproducibility. The diagnostic value of the extrapolated AADI was high for aAAS (sensitivity 92%; specificity of 100%) and severe aAAS (sensitivity75%; specificity 100%). The diagnostic value of the extrapolated PADI was good but lower than the diagnostic value of the extrapolated AADI. CONCLUSION: Extrapolated AADI can be used instead AADI to detect aAAS and severe aAAS.

Tocilizumab controls bone turnover in early polymyalgia rheumatica.

OBJECTIVES: This study explores changes in the bone homeostasis by testing the N-terminal collagen type I extension propeptide (PINP) marker for osteo-formation and the carboxy-terminal region of collagen type I (CTX-I) marker for osteo-resorption in patients taking tocilizumab for polymyalgia rheumatica (PMR). METHODS: Twenty patients were included in the prospective open-label TENOR study (Clinicaltrials.gov NCT01713842) and received three monthly tocilizumab infusions, followed by corticosteroids starting at week (W) 12. PINP and CTX-I were tested at inclusion (W0), after tocilizumab but before steroid initiation (W12), at the end of the protocol (W24) and were compared to healthy controls. Information regarding disease activity, bone mineral density using scanographic bone attenuation correlation (SBAC), inflammatory parameters and interleukin (IL)-6 levels were collected during the follow-up of the patients. RESULTS: PMR patients were characterised by a reduction in bone mineral density and a higher level of CTX-I relative to healthy controls matched in age and sex at baseline. PINP levels increased at W12 (P< 0.001, versus W0) following tocilizumab introduction and CTX-I levels decreased at W24 and after steroid initiation (P=0.001, versus W0). Such modifications explain the altered correlation observed between PINP and CTX-I at W0 (r=0.255 at W0 versus r=0.641 in healthy controls) and its correction after treatment (r=0.760 at W12 and r=0.767 at W24). Finally, greater changes in PINP were observed in patients whose circulating IL-6 levels decreased after tocilizumab therapy. CONCLUSIONS: Control of bone turnover, in part through the inhibition of the IL-6 axis, is observed during tocilizumab and subsequent steroid treatment of PMR.

Associations of lumbar scoliosis with presentation of suspected early axial spondyloarthritis.

OBJECTIVE: Scoliosis may impact the mechanical loading and cause secondary changes of the sacroiliac joints and lumbar spine. Our goal was to look how lumbar scoliosis modify the clinical and imaging-study in patients with recent-onset inflammatory back pain (IBP) suggesting axial spondyloarthritis (axSpA). METHODS: Baseline weight-bearing lumbar-spine radiographs obtained in the DESIR cohort of patients aged 18-50 years and having IBP for at least 3 months but less than 3 years suggesting axSpA were studied. After training on scoliosis detection based on Cobb's angle>10° plus Nash-Moe grade≥1, readers blinded to patient data measured spine lumbar scoliosis, sacral horizontal angle, lumbosacral angle and lumbar lordosis on the radiograph of the lumbar and scored sacroiliitis on the radiograph of the pelvis. Baseline MRIs T1 and STIR of the lumbar spine and sacroiliac joints were evaluated for respectively degenerative changes and signs of axSpA. RESULTS: Of the 360 patients (50.8% females) 88.7% had lumbar pain and 69.3% met ASAS criteria for axSpA. Mean Cobb's angle was 3.2°±5.0° and 28 (7.7%) patients had lumbar scoliosis. No statistical differences were observed for radiographic sacroiliitis, MRI sacroiliitis, modified Stoke Ankylosing Spondylitis Spinal Score, Pfirmmann score, high-intensity zone, protrusion, extrusion, MODIC score between patients with and without scoliosis. In both groups, degenerative changes by MRI were rare and predominated at L4-L5 and L5-S1. CONCLUSION: In patients with early IBP suggesting axSpA, lumbar scoliosis was not associated with inflammatory or degenerative changes.

Localized Myofascial Inflammation Revealed by Magnetic Resonance Imaging in Recent-onset Polymyalgia Rheumatica and Effect of Tocilizumab Therapy.

OBJECTIVE: To assess the prevalence of myofascial inflammatory lesions visible by magnetic resonance imaging (MRI) and their changes after tocilizumab (TCZ) therapy in active polymyalgia rheumatica (PMR). METHODS: We conducted a posthoc analysis of data from the TENOR study of TCZ monotherapy in PMR. The 18 patients each received TCZ injections at weeks 0, 4, and 8. The shoulder and pelvic girdles were assessed at baseline then at weeks 2 and 12 using T1- and T2- short-tau inversion recovery-weighted MRI. Radiologists blinded to patient data assessed each muscle group for localized myofascial inflammation on baseline, Week 2, and Week 12 MRI. Reproducibility was estimated by having 2 radiologists assess the Week 2 MRI of 13 patients, then computing the κ coefficient. RESULTS: For myofascial lesion detection, intraobserver reproducibility was almost perfect (κ = 0.890) and interobserver reproducibility was substantial (κ = 0.758). At baseline, all patients had at least 1 inflammatory myofascial lesion; sites involved were the shoulder in 10 (71.4%) patients, hip in 13 (86.7%), ischial tuberosity in 9 (60.0%), and pubic symphysis in 12 (80.0%). Sites involved at Week 12 were the shoulder in 8 patients (53.3%), hip in 5 (33.3%), ischial tuberosity in 1, and pubic symphysis in 3 (20.0%). At Week 12, of 103 muscle groups studied in all, 43 (41.7%) had no inflammatory lesions, compared to 33 at baseline (p = 0.002); improvements were noted in 66 (64.1%) muscle groups, worsening in 2 (1.9%), no change in 35 (34.0%; p = 0.034). CONCLUSION: Localized myofascial inflammatory lesions are common in recent-onset PMR and improve during TCZ therapy. Clinicaltrials.gov (NCT01713842).

Ultrasonography and magnetic resonance imaging changes in patients with polymyalgia rheumatica treated by tocilizumab.

BACKGROUND: This study assessed inflammatory changes using ultrasound (US) and magnetic resonance imaging (MRI) in patients taking tocilizumab for polymyalgia rheumatica (PMR). METHODS: Eighteen patients were included in the prospective open-label TENOR study and received three tocilizumab infusions, without corticosteroids. B-mode and power Doppler US and MRI (T1 and T2-short time inversion recuperation weighted sequences) of the hips and shoulders were performed at weeks 0, 2, and 12. Subacromial, trochanteric, and iliopsoas bursitis and intraarticular glenohumeral and coxofemoral effusions/synovitis were scored from 0 to 3. Changes over time and US-MRI correlations were evaluated. RESULTS: At baseline, the proportions of shoulders and hips with bursitis were 93 and 100% by MRI and 61 and 13% by US; and the corresponding proportions for intraarticular effusions/synovitis were 100 and 100% by MRI and 57 and 53% by US. Imaging findings did not improve during the first two treatment weeks. From baseline to week 12, bursitis improved significantly at all four joints by MRI (P = 0.005) and US (P = 0.029) and intraarticular effusions/synovitis by US only (P = 0.001). The proportion of abnormalities that improved by week 12 was 42% by MRI and 37% by US. MRI detected bursitis in a larger proportion of hips (73% versus 13%) and US in a larger proportion of shoulders (57% versus 28%), whereas no difference was found for intraarticular effusions/synovitis. At baseline, agreement between US and MRI findings was poor. CONCLUSIONS: US and MRI showed significant improvements in inflammatory lesions during tocilizumab treatment of PMR.

Concordance between clinical and ultrasound findings in rheumatoid arthritis.

BACKGROUND: Clinical joint examination is less time-consuming than ultrasound in rheumatoid arthritis. Knowledge of clinical and ultrasound concordance of joints groups could help in selecting joints for a best ultrasonographic assessment. OBJECTIVE: To evaluate concordance between clinical examination and ultrasound of joints in a heterogeneous group of patients with rheumatoid arthritis. METHOD: Forty patients were included in a prospective, transversal, single-center study, whatever disease activity, duration or treatment. In each patient, 40 joints were evaluated for a total of 1600 joints. Synovitis was scored using clinical examination, B-mode, power Doppler and both B-mode and power Doppler. Concordance between swelling joint by clinical examination, synovitis thickening by B-mode (grade 1 or higher) and inflammation by power Doppler (grade 1 or higher) was assessed by computing the kappa coefficient. RESULTS: Clinical joint examination and ultrasound concordance was very low at the shoulders and metatarsophalangeal joints (κ < 0.1) and was low at wrists (κ: 0.23 to 0.30). B-mode and power Doppler found 2.4 and 1.4 more synovitis than swollen joint count using clinical examination and up to 30 times more at metatarsophalangeal joints. Concordance was strong at tibio-talar joints (κ: 0.65 to 0.82) and moderate at others joints sites (κ: 0.4 to 0.6). CONCLUSION: Assessment of a heterogeneous group showed that ultrasound adds information to clinical examination, most notably at the shoulders, wrists and metatarsophalangeal joints. Concordance was moderate to strong at other joint sites.