Fatigue in spondyloarthritis: a marker of disease activity. A cross-sectional study of 266 patients.

OBJECTIVES: Fatigue is an important aspect of spondyloarthritis (SpA). However the influencing factors of fatigue in SpA are unclear. The objective of this study was to explore if fatigue is related to disease activity or to patient characteristics. METHODS: This was a retroelective observational study (Cochin COSPA study) in one tertiary-referral centre. The primary outcome was fatigue, evaluated on a 0-100mm Visual Analogue Scale (VAS). The covariates were demographic characteristics, disease subtype (axial vs. peripheral) and disease-related factors, e.g. Bath Disease Activity Index (BASDAI), patient global assessment (VAS), Bath Functional Index (BASFI). To explain fatigue, univariate then multivariate logistic regressions were conducted (with fatigue analysed as above or below 50 mm), as well as multiple linear regressions with the different covariates. RESULTS: Two hundred and sixty-six SpA patients were analysed. Sixty-one percent were male; mean age and disease duration were 44.5±13.5 years and 16.8±11.7 years, respectively. Mean VAS fatigue was 49.3±32.7mm; 49.6% of patients had fatigue VAS>50mm. Logistic regression showed high fatigue was associated with disease: BASDAI and BASFI (p<0.0001), as well as female gender (p=0.025) and aerobic exercise (p=0.005), but there was no difference in the subtypes of SpA. In multivariate analysis, the single factor explaining fatigue was patient global assessment (p<0.001 and odds ratio =1.35). By linear regression, demographic variables explained 2.8% of the variance, whereas disease characteristics and activity explained 44.6%. CONCLUSIONS: Fatigue levels were high in SpA patients whatever the subtype and appeared more strongly related to the disease than to patient-related variables, thus confirming its usefulness as an outcome measure.

Assessment of work instability in spondyloarthritis: a cross-sectional study using the ankylosing spondylitis work instability scale.

OBJECTIVES: Work status is an important outcome in SpA. The objective was to assess work instability and its determinants in a cohort of patients with SpA, using the AS-work instability scale (AS-WIS). METHODS: We performed a cross-sectional monocentre study. Patients were definite SpA patients with paid work. Work instability was measured by the AS-WIS. Its determinants were assessed by correlations with SpA scores (BASDAI, BASFI and patient's global assessment) and patients with low work instability (AS-WIS score < 11) were compared with those with moderate to high instability, through backward logistic regression. RESULTS: In all, 156 patients were assessed: mean (s.d.) age 41 (11) years, mean disease duration 15 (11) years; 71 (45.5%) were on TNF blockers. The mean AS-WIS score was 9.5 (5.5); 55 (35%) patients had moderate and 8 (5%) patients had high work instability. Correlations of the AS-WIS score with SpA scores were significant but moderate (BASDAI R = 0.42, BASFI R = 0.41, patient's global assessment R = 0.53; P < 0.0001). In multivariate analysis, high patient's global assessment was the only element associated with moderate to high work instability; demographic characteristics and treatments were not significant elements. CONCLUSION: Work instability was found to be high and its main determinant was patient's global assessment. The predictive validity of the AS-WIS in terms of job retention should be further assessed.

Prevalence and clinical characteristics of dactylitis in spondylarthritis: a descriptive analysis of 275 patients.

OBJECTIVES: Dactylitis is a common but little studied feature of spondylarthritis (SpA). Our objective was to assess the prevalence of dactylitis among a cohort of patients with spondylarthritis in a tertiary care centre and to describe the clinical characteristics of dactylitis. METHODS: This was a prospective single centre observational study carried out in 2010. The patients included had been diagnosed as having definite SpA based on Amo's criteria. Each patient was interviewed by a physician. The data collected included prevalence of dactylitis and its clinical characteristics, effectiveness of the different treatments, and association with severe manifestations of SpA, and analysed by descriptive analysis. RESULTS: 275 consecutive SpA patients were assessed: mean age 43.2±13.5 years, mean disease duration 14.0±11.8 years, 169 (61.4%) were men. In all, 59 patients (21.5%) suffered from SpA-associated dactylitis. The localisation of dactylitis was toes in 46 patients (78.0%) and/or fingers in 25 patients (42.4%). The most frequent localisations were the second toe and the second finger. Dactylitis was the first symptom of SpA in 14 patients (5.1%), and 28.8% (n=17) of dactylitis appeared within the first 5 years of disease. Dactylitis was present in 35.1% (n=13) of patients with undifferenciated SpA and in 30.6% (n=15) of patients with psoriatic arthritis. It was significantly associated with history of peripheral arthritis or heel pain. In our population, there was no correlation between dactylitis and HLA B27 status or sex and it was not a marker of severity of disease. CONCLUSIONS: Dactylitis is a frequent manifestation in SpA (21.5%) particularly in peripheral disease and it may be the first manifestation of the disease with localisation being more frequent in the toes.

Heel pain in spondyloarthritis: results of a cross-sectional study of 275 patients.

OBJECTIVES: Heel pain is a common but poorly studied feature of spondyloarthritis (SpA). The aims of this study were to assess the prevalence and clinical features of heel pain in a cohort of patients with SpA. METHODS: This was a retrolective single centre observational study in 2010. Patients with SpA as defined by Amor's criteria were recruited. The data collected were: demographic and disease characteristics, history of heel pain, age at first heel pain, localisation, nature and intensity of pain and treatments. The analyses were descriptive. RESULTS: A total of 275 SpA patients (mean age 44.6±13.5 yrs, mean disease duration 16.7±11.8 yrs, 61.5% men) were assessed. A history of heel pain was reported in 130 patients (47.1%), and was the first symptom of SpA in 15.7% of all patients. Heel pain was frequent in both axial (89/201, 44.3%) and peripheral disease (27/56, 48.2%). Distribution was more frequently inferior (88, 69.3%) than posterior (61, 48.0%) (p<0.0001), and frequently bilateral: simultaneously (41.9%) rather than alternatively (29.1%) (p=0.03). Main clinical symptoms were: morning pain on weight bearing (83.6%), but also night pain (34.4%), and/or patient-described swelling (24.2%). Heel pain was frequently recurrent (74.2%), intense (70.3%), source of a limp (71.6%), and often resistant to non-steroidal anti-inflammatory drugs (NSAIDs) (54/108, 50%). Tumour necrosis factor blockers were efficacious on heel pain in 72/94 (76.6%) of cases. CONCLUSIONS: This study confirmed heel pain as a frequent symptom in both axial and peripheral SpA. It occurred early in the disease course and it was frequently recurrent and resistant to NSAIDs.

Prevalence and characteristics of hip involvement in spondyloarthritis: a single-centre observational study of 275 patients.

OBJECTIVES: Hip involvement is a classic feature of spondyloarthritis (SpA). The aim of the present paper is to study the prevalence, clinical and radiological features of hip involvement, and the association with criteria for severity, in a cohort of patients with SpA in a tertiary care centre. DESIGN: retrospective single centre observational study in 2010 of patients with definite SpA who underwent direct interview by a physician. Hip involvement was defined as hip pain considered related to SpA inflammation and confirmed radiographically. Other data collection: demographic data, SpA characteristics, treatments performed for hip involvement. ANALYSIS: prevalence of hip involvement was analysed according to disease duration (Kaplan-Meyer). Multivariate Cox analysis compared patients with vs. without hip involvement over time. RESULTS: In all, 275 SpA patients were assessed. The median age was 45 (IQR 35-55) years, the median SpA symptom duration 14 (7-25) years, 61% (169) were men, and 79% were HLA-B27 positive. Hip involvement was found in 18% (49) SpA patients, with already 13% after 5 years of disease duration and with frequent bilateral involvement (61%). Hip involvement was associated with non-Caucasian origin (p=0.05). Thirty-three percent (16/49) needed surgery (23 total joint replacements in all) with good functional results. CONCLUSIONS: Hip involvement is a frequent manifestation in SpA (18%), often bilateral, and associated with non-Caucasian origin. One third of the patients needed total joint replacement. Physicians should be wary of hip pain in SpA patients and implement rapid diagnostic procedures in such cases.

Azithromycin reduces exaggerated cytokine production by M1 alveolar macrophages in cystic fibrosis.

Macrophages phagocyte pathogenic microorganisms and orchestrate immune responses by producing a variety of inflammatory mediators. The cystic fibrosis (CF) transmembrane conductance regulator chloride channel has been reported to be of pivotal importance for macrophage functions. The exact phenotype and role of macrophages in CF is still unknown. Alveolar and peritoneal macrophages were monitored in CF mice homozygous for the F508 del mutation and in wild-type control animals. Classical (M1) and alternative (M2) macrophage polarization and responses to LPS from Pseudomonas aeruginosa were investigated, and the effect of azithromycin was examined in both cell populations. We show that alveolar macrophage counts were 1.7-fold higher in CF as compared with wild-type mice. The macrophage-related chemokine, chemokine C-C motif ligand (CCL)-2, was found to be at least 10-fold more abundant in the alveolar space of mutant mice. Cell count and CCL-2 protein levels were also increased in the peritoneal cavity of CF mice. Both M1 and M2 macrophage polarization were significantly enhanced in alveolar and peritoneal cells from F508del-CF mice as compared with control animals. LPS-stimulated expression of proinflammatory mediators, such as nitric oxide synthase-2, IL-1beta, and CCL-2, was increased, whereas anti-inflammatory IL-10 expression was decreased in CF macrophages. Azithromycin, added to cell cultures at 1 mg/liter, significantly reduced proinflammatory cytokine expression (IL-1beta, CCL-2, TNF-alpha) in M1-induced CF and wild-type alveolar macrophages. Our findings indicate that CF macrophages are ubiquitously accumulated, and that these cells are polarized toward classical and alternative activation status. Azithromycin down-regulates inflammatory cytokine production by M1-polarized CF alveolar macrophages.

Serum level of adiponectin is a surrogate independent biomarker of radiographic disease progression in early rheumatoid arthritis: results from the ESPOIR cohort.

INTRODUCTION: Adipokines such as adiponectin, leptin, and visfatin/nicotinamide phosphoribosyltransferase (NAMPT) have recently emerged as pro-inflammatory mediators involved in the pathophysiology of rheumatoid arthritis (RA). We aimed to determine whether serum adipokine levels independently predicted early radiographic disease progression in early RA. METHODS: In total, 791 patients were included from the prospective Etude et Suivi des POlyarthrites Indifférenciées Récentes (ESPOIR) cohort who met the American College of Rheumatology-European League Against Rheumatism criteria for RA (n = 632) or had undifferentiated arthritis (UA) (n = 159). Enzyme-linked immunosorbent assay (ELISA) was used to assess baseline serum levels of adiponectin, leptin, and visfatin/NAMPT. In the RA group, we tested the association of serum adipokine levels and (a) baseline radiographic damage and (b) radiographic disease progression, defined as a change >0 or ≥ 5 in total Sharp-van der Heijde Score (∆SHS) between inclusion and 1 year (∆SHS ≥1 or rapid radiographic progression: ∆SHS ≥5), adjusting for confounders (age, sex, body-mass index, insulin resistance, C-reactive protein level, Disease Activity Score in 28 joints, Health Assessment Questionnaire score, autoantibody status, steroid use, and radiographic evidence of RA damage at inclusion). RESULTS: Adiponectin level was independently associated with baseline total SHS (adjusted ß = 0.12; P = 0.006). It was also associated with ∆SHS ≥1 (adjusted odds ratio (aOR) = 1.84 (1.25 to 2.72)) involving erosive as well as narrowing disease progression (aOR = 1.73 (1.17 to 2.55) and 1.93 (1.04 to 3.57), respectively). Serum adiponectin level predicted ∆SHS ≥5 (aOR = 2.0 (1.14 to 3.52)). Serum leptin level was independently associated only with ∆SHS >0 (aOR = 1.59 (1.05 to 2.42)). Conversely, serum visfatin/NAMPT level and radiographic disease progression were unrelated. Considering the receiver-operated characteristic curves, the best adiponectin cut-offs were 4.14 µg/ml for ∆SHS ≥1 and 6.04 µg/ml for ∆SHS ≥5, with a good specificity (58% and 75% for ∆SHS ≥1 and ∆SHS ≥5, respectively) and high negative predictive values (75% and 92% for ∆SHS ≥1 or ∆SHS ≥5, respectively). CONCLUSION: Serum adiponectin level is a simple useful biomarker associated with early radiographic disease progression in early RA, independent of RA-confounding factors and metabolic status.

Clinical characteristics of anterior chest wall pain in spondyloarthritis: an analysis of 275 patients.

OBJECTIVES: Anterior chest wall pain is a common but little studied feature of spondyloarthritis. The objectives of our study were to assess the prevalence of anterior chest wall pain and to describe its clinical characteristics in a cohort of spondyloarthritis patients in a tertiary care center. STUDY DESIGN: retrolective single center observational study in 2010 (COSPA). Consecutive patients with definite spondyloarthritis according to Amor's criteria were included. DATA COLLECTION: each patient underwent direct interview by a physician. Prevalence of anterior chest wall pain, according to spondyloarthritis subtype and its date of appearance, localization and nature were collected. RESULTS: In all, 275 consecutive spondyloarthritis patients were assessed. Among them, 102 patients (37.1%) suffered from spondyloarthritis-associated anterior chest wall pain. It was the first symptom of spondyloarthritis in 3.6% of cases. The prevalence after 5 and 10 years following the diagnosis of spondyloarthritis was 26.0% and 35.5%, respectively. Pain was usually in the upper chest and acute, increased by respiratory movements and movements of the arm; pain during the night was less frequent (41.0%). A flare lasted on average 5 weeks; recurrences were frequent (75%). Non-steroidal anti-inflammatory drugs and anti-tumor necrosis factor agents were reported as effective in 49.3% and 80.0% of cases, respectively. CONCLUSION: Anterior chest wall pain was a frequent manifestation in spondyloarthritis. It occurred early in the disease course, but the risk persisted after disease onset. Better knowledge of the clinical characteristics of this symptom may help physicians for diagnosis and follow-up.

Performance of the assessment in Spondyloarthritis International Society classification for axial and peripheral spondyloarthritis in an established clinical cohort: comparison with criteria sets of Amor and the European Spondylarthropathy Study Group.

OBJECTIVE: To evaluate the performance of the Assessment in Spondyloarthritis International Society (ASAS) criteria (axial or peripheral) against the Amor and European Spondylarthropathy Study Group criteria in established spondyloarthritis (SpA). METHODS: Rheumatologist-diagnosed patients with SpA were retrospectively classified according to the different criteria sets. Clinical characteristics of patients fulfilling all 3 criteria were compared with those who did not, by nonparametric statistics. RESULTS: ASAS classified 90% of the 231 patients, with 169 (73%) fulfilling all 3 criteria sets. Multivariate analysis showed the 62 patients not fulfilling all criteria sets were older at symptom onset (p < 0.001) and less likely to have inflammatory back pain (p < 0.001), peripheral arthritis (p < 0.001), or elevated C-reactive protein levels (p = 0.034). CONCLUSION: ASAS criteria can be used in established disease.

Azithromycin fails to reduce increased expression of neutrophil-related cytokines in primary-cultured epithelial cells from cystic fibrosis mice.

BACKGROUND: Beneficial effects of azithromycin in cystic fibrosis (CF) have been reported, however, its mechanism of action remains unclear. The present study aimed at investigating the effect of azithromycin on CF airway epithelial cells. METHODS: Primary cultures of purified tracheal epithelial cells from F508del and normal homozygous mice were established. Responses to lipopolysaccharide from Pseudomonas aeruginosa (LPS, 0.1 microg/ml) on mRNA expression of neutrophil-related chemokines, pro- and anti-inflammatory cytokines were investigated in the presence or the absence of azithromycin (1 microg/ml). RESULTS: CF airway epithelial cells showed upregulation of MIP-2 and KC responses to LPS, and azithromycin failed to downregulate these responses. In contrast, in CF cells, azithromycin increased KC and TNF-alpha expression under non-stimulated and LPS-stimulated conditions, respectively. In non-CF cells, the macrolide potentiated the LPS response on MIP-2 and on IL-10. CONCLUSIONS: Airway epithelial cells contribute to the dysregulated immune processes in CF. Azithromycin rather stimulates cytokine expression in CF airway epithelial cells.