Targeting Common Inflammatory Mediators in Experimental Severe Asthma and Acute Lung Injury.

Neutrophils, known to be mobilized and activated in high amounts through Il-17 stimulation, are a key factor for clinical manifestation and imbalance of redox systems favoring a dominant oxidative state in both severe asthma and acute lung injury (f). The aim of this study was to evaluate in mice, the effect of Secukinumab (SECU) in a model of ovalbumin-induced asthma exacerbated with LPS administration to induce ALI, compared to dexamethasone (DEXA), already known for its benefit in both asthma and ALI. Results on cytokine levels for specific Th1, Th2 and Th17 revealed an interplay of immune responses. For Th1 effector cytokines in BALF, DEXA treatment increased TNF-α levels, but TNF-α was not modified by SECU; DEXA and SECU significantly decreased IFN-γ and IL-6 levels. For typical Th2 cytokines, DEXA significantly increased Il-4, Il-5 and Il-13 levels, while SECU significantly inhibited Il-5 levels. Both SECU and DEXA significantly decreased Il-17 levels. Cytokine level changes in lung tissue homogenate were partly similar to BALF cytokines. Conclusion: in addition to DEXA, SECU possesses the ability to modulate inflammatory cytokine release and to decrease Th17 responses in ALI overlapped on exacerbated asthma in mice.

24 h Holter ECG Monitoring of Patients with Rheumatoid Arthritis-A Potential Role for a Precise Evaluation of QT Interval Duration and Associated Arrhythmic Complications.

Background: Patients with rheumatoid arthritis (RA) have increased systemic inflammatory burden associated with elevated cardiovascular mortality. Prolonged ventricular repolarisation evaluated by QT interval duration is a risk factor for cardiovascular and total mortality. In RA, mortality risk is correlated with dynamics and cumulative incidence of QTc prolongation rather than QTc value. The aim is to evaluate if QT parameters evaluated with 24 h Holter ECG are a better option to complete the cardiovascular profile of RA patients than parameters from short ECG recordings. Materials and methods: A total of 58 patients (22 males, 36 females) with RA were submitted to short ECG recordings at admission and to 24 h Holter ECG. QT interval parameters and ventricular ectopy generated from both types of recordings were analyzed. Results: QTc interval values obtained from Holter ECG were significantly higher than the values from short term ECG and were correlated with severity of inflammatory process. The number of QRS complexes with QTc > 450 ms recorded during 24 h Holter was strongly correlated with the number of ventricular events and severity of the inflammatory process. Conclusions: In patients with RA, the Holter ECG recordings could realize a more precise evaluation of the extent and dynamics of QTc interval duration and of ventricular ectopic events with potential risk of sudden death.

QT Interval Prolongation in Patients with Systemic Sclerosis-Are the Holter ECG Recordings a Better Option for QT Interval Evaluation?

Background and Objectives: Cardiac involvement in systemic sclerosis has important consequences on patient survival. Myocardial fibrosis and microcirculation involvement can generate arrhythmic complications, which can be associated with a higher death risk. QT interval prolongation is considered as a risk factor for ectopic ventricular events and can be evaluated using standard short ECG recordings or 24-h Holter ECG recordings. Materials and Methods: 39 patients with systemic sclerosis were submitted to a standard ECG recording at admission and 24-h Holter ECG monitoring. Results: QT interval values resulted from Holter ECG monitoring are higher than the values generated by the short-term ECG recordings. Holter ECG monitoring permits the detection of ventricular ectopy in patients with no events on standard ECG. Conclusions: In patients with systemic sclerosis, 24-h Holter ECG recordings can realize a more precise evaluation of the extent of QTc interval prolongation and ventricular ectopic events associated with myocardial involvement.

Treatment Satisfaction, Patient Preferences, and the Impact of Suboptimal Disease Control in a Large International Rheumatoid Arthritis Cohort: SENSE Study.

BACKGROUND: Patients' needs and perspectives are important determinants of treatment success in rheumatoid arthritis (RA). Assessing patients' perspectives can help identify unmet needs and enhance the understanding of treatment benefits. OBJECTIVE: The SENSE study assessed the impact of inadequate response to disease-modifying antirheumatic drugs (DMARDs) on treatment satisfaction, disease outcomes, and patient perspectives related to RA disease management. METHODS: SENSE was a noninterventional, cross-sectional study conducted in 18 countries across Europe, Asia, and South America. Adult patients with poorly controlled RA of moderate/high disease activity were eligible. Patient satisfaction was assessed by the Treatment Satisfaction Questionnaire for Medication (TSQM v1.4). Treatment adherence, healthcare resource utilization (HRU), quality of life (QoL), work ability, digital health literacy (DHL), patient preference information, and treatment strategy were also assessed. RESULTS: A total of 1624 patients were included in the study: most were female (84.2%) and middle-aged, and mean disease duration was 10.5 years. Mean TSQM global satisfaction subscore was 60.9, with only 13.5% of patients reporting good treatment satisfaction (TSQM global ≥80). The strongest predictor of good treatment satisfaction was treatment with advanced therapies. Most patients (87.4%) reported good treatment adherence. In general, patients had impaired QoL and work ability, high HRU, and 67.4% had poor DHL. Leading treatment expectations were "general improvement of arthritis" and "less joint pain". Most patients preferred oral RA medications (60.7%) and rapid (≤1 week) onset of action (71.1%). "Increased risk for malignancies" and "increased risk for cardiovascular disease" were the least acceptable side effects. Despite suboptimal control, advanced therapies were only used in a minority of patients, and DMARD switches were planned for only half of the patients. CONCLUSION: Suboptimal disease control negatively impacts treatment satisfaction, work ability, QoL, and HRU. Data collected on patient perspectives may inform shared decision-making and optimize treat-to-target strategies for improving patient outcomes in RA.

Outcomes of patients with systemic sclerosis treated with rituximab in contemporary practice: a prospective cohort study.

OBJECTIVE: To assess the safety and efficacy of rituximab in systemic sclerosis (SSc) in clinical practice. METHODS: We performed a prospective study including patients with SSc from the European Scleroderma Trials and Research (EUSTAR) network treated with rituximab and matched with untreated patients with SSc. The main outcomes measures were adverse events, skin fibrosis improvement, lung fibrosis worsening and steroids use among propensity score-matched patients treated or not with rituximab. RESULTS: 254 patients were treated with rituximab, in 58% for lung and in 32% for skin involvement. After a median follow-up of 2 years, about 70% of the patients had no side effect. Comparison of treated patients with 9575 propensity-score matched patients showed that patients treated with rituximab were more likely to have skin fibrosis improvement (22.7 vs 14.03 events per 100 person-years; OR: 2.79 [1.47-5.32]; p=0.002). Treated patients did not have significantly different rates of decrease in forced vital capacity (FVC)>10% (OR: 1.03 [0.55-1.94]; p=0.93) nor in carbon monoxide diffusing capacity (DLCO) decrease. Patients having received rituximab were more prone to stop or decrease steroids (OR: 2.34 [1.56-3.53], p<0.0001). Patients treated concomitantly with mycophenolate mofetil had a trend for better outcomes as compared with patients receiving rituximab alone (delta FVC: 5.22 [0.83-9.62]; p=0.019 as compared with controls vs 3 [0.66-5.35]; p=0.012). CONCLUSION: Rituximab use was associated with a good safety profile in this large SSc-cohort. Significant change was observed on skin fibrosis, but not on lung. However, the limitation is the observational design. The potential stabilisation of lung fibrosis by rituximab has to be addressed by a randomised trial.

Patterns and predictors of skin score change in early diffuse systemic sclerosis from the European Scleroderma Observational Study.

OBJECTIVES: Our aim was to use the opportunity provided by the European Scleroderma Observational Study to (1) identify and describe those patients with early diffuse cutaneous systemic sclerosis (dcSSc) with progressive skin thickness, and (2) derive prediction models for progression over 12 months, to inform future randomised controlled trials (RCTs). METHODS: The modified Rodnan skin score (mRSS) was recorded every 3 months in 326 patients. 'Progressors' were defined as those experiencing a 5-unit and 25% increase in mRSS score over 12 months (±3 months). Logistic models were fitted to predict progression and, using receiver operating characteristic (ROC) curves, were compared on the basis of the area under curve (AUC), accuracy and positive predictive value (PPV). RESULTS: 66 patients (22.5%) progressed, 227 (77.5%) did not (33 could not have their status assessed due to insufficient data). Progressors had shorter disease duration (median 8.1 vs 12.6 months, P=0.001) and lower mRSS (median 19 vs 21 units, P=0.030) than non-progressors. Skin score was highest, and peaked earliest, in the anti-RNA polymerase III (Pol3+) subgroup (n=50). A first predictive model (including mRSS, duration of skin thickening and their interaction) had an accuracy of 60.9%, AUC of 0.666 and PPV of 33.8%. By adding a variable for Pol3 positivity, the model reached an accuracy of 71%, AUC of 0.711 and PPV of 41%. CONCLUSIONS: Two prediction models for progressive skin thickening were derived, for use both in clinical practice and for cohort enrichment in RCTs. These models will inform recruitment into the many clinical trials of dcSSc projected for the coming years. TRIAL REGISTRATION NUMBER: NCT02339441.

Disability, fatigue, pain and their associates in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study.

Objectives: Our aim was to describe the burden of early dcSSc in terms of disability, fatigue and pain in the European Scleroderma Observational Study cohort, and to explore associated clinical features. Methods: Patients completed questionnaires at study entry, 12 and 24 months, including the HAQ disability index (HAQ-DI), the Cochin Hand Function Scale (CHFS), the Functional Assessment of Chronic Illness Therapy-fatigue and the Short Form 36 (SF36). Associates examined included the modified Rodnan skin score (mRSS), current digital ulcers and internal organ involvement. Correlations between 12-month changes were also examined. Results: The 326 patients recruited (median disease duration 11.9 months) displayed high levels of disability [mean (s.d.) HAQ-DI 1.1 (0.83)], with 'grip' and 'activity' being most affected. Of the 18 activities assessed in the CHFS, those involving fine finger movements were most affected. High HAQ-DI and CHFS scores were both associated with high mRSS (ρ = 0.34, P < 0.0001 and ρ = 0.35, P < 0.0001, respectively). HAQ-DI was higher in patients with digital ulcers (P = 0.004), pulmonary fibrosis (P = 0.005), cardiac (P = 0.005) and muscle involvement (P = 0.002). As anticipated, HAQ-DI, CHFS, the Functional Assessment of Chronic Illness Therapy and SF36 scores were all highly correlated, in particular the HAQ-DI with the CHFS (ρ = 0.84, P < 0.0001). Worsening HAQ-DI over 12 months was strongly associated with increasing mRSS (ρ = 0.40, P < 0.0001), decreasing hand function (ρ = 0.57, P < 0.0001) and increasing fatigue (ρ = -0.53, P < 0.0001). Conclusion: The European Scleroderma Observational Study highlights the burden of disability in early dcSSc, with high levels of disability and fatigue, associating with the degree of skin thickening (mRSS). Impaired hand function is a major contributor to overall disability.

Functional disability and its predictors in systemic sclerosis: a study from the DeSScipher project within the EUSTAR group.

Objectives: The multisystem manifestations of SSc can greatly impact patients' quality of life. The aim of this study was to identify factors associated with disability in SSc. Methods: SSc patients from the prospective DeSScipher cohort who had completed the scleroderma health assessment questionnaire (SHAQ), a disability score that combines the health assessment questionnaire and five visual analogue scales, were included in this analysis. The effect of factors possibly associated with disability was analysed with multiple linear regressions. Results: The mean SHAQ and HAQ scores of the 944 patients included were 0.87 (s.d. = 0.66) and 0.92 (s.d. = 0.78); 59% of the patients were in the mild to moderate difficulty SHAQ category (0 ⩽ SHAQ < 1), 34% in the moderate to severe disability category (1 ⩽ SHAQ < 2) and 7% in the severe to very severe disability category (2 ⩽ SHAQ ⩽ 3). The means of the visual analogue scales scores were in order of magnitude: overall disease severity (37 mm), RP (31 mm), pulmonary symptoms (24 mm), gastrointestinal symptoms (20 mm) and digital ulcers (19 mm). In multiple regression, the main factors associated with high SHAQ scores were the presence of dyspnoea [modified New York Heart Association (NYHA) class IV (regression coefficient B = 0.62), modified NYHA class III (B = 0.53) and modified NYHA class II (B = 0.21; all vs modified NYHA class I)], FM (B = 0.37), muscle weakness (B = 0.27), digital ulcers (B = 0.20) and gastrointestinal symptoms (oesophageal symptoms, B = 0.16; stomach symptoms, B = 0.15; intestinal symptoms, B = 0.15). Conclusion: SSc patients perceive dyspnoea, pain, digital ulcers, muscle weakness and gastrointestinal symptoms as the main factors driving their level of disability, unlike physicians who emphasize objective measures of disability.

Intercentre variance in patient reported outcomes is lower than objective rheumatoid arthritis activity measures: a cross-sectional study.

Objective: To assess intercentre variability in the ACR core set measures, DAS28 based on three variables (DAS28v3) and Routine Assessment of Patient Index Data 3 in a multinational study. Methods: Seven thousand and twenty-three patients were recruited (84 centres; 30 countries) using a standard protocol in the Quantitative Standard Monitoring of Patients with RA study. Analysis of variance (ANOVA) and mixed-effect analysis of covariance models were used to model the relationship between study centre and different patient-reported and physician-reported RA activity measures. These models were built to adjust for the remaining ACR core set measure (for each ACR core set measure or each composite index), socio-demographics and medical characteristics. ANOVA and analysis of covariance models yielded similar results, and ANOVA tables were used to present variance attributable to recruiting centre. Results: The proportion of variances attributable to recruiting centre was lower for patient reported outcomes (PROs: pain, HAQ, patient global) compared with objective measures (joint counts, ESR, physician global) in all models. In the full model, variance in PROs attributable to recruiting centre ranged from 1.53% for patient global to 3.71% for HAQ compared with objective measures that ranged from 5.92% for physician global to 9.25% for ESR; and was lower for Routine Assessment of Patient Index Data 3 (2.6%) compared with DAS28v3 (11.75%). Conclusion: Intercentre variability in PROs is lower than objective measures of RA activity demonstrating that PROs may be more comparable across centres, and the need for standardization of objective measures.

Treatment outcome in early diffuse cutaneous systemic sclerosis: the European Scleroderma Observational Study (ESOS).

OBJECTIVES: The rarity of early diffuse cutaneous systemic sclerosis (dcSSc) makes randomised controlled trials very difficult. We aimed to use an observational approach to compare effectiveness of currently used treatment approaches. METHODS: This was a prospective, observational cohort study of early dcSSc (within three years of onset of skin thickening). Clinicians selected one of four protocols for each patient: methotrexate, mycophenolate mofetil (MMF), cyclophosphamide or 'no immunosuppressant'. Patients were assessed three-monthly for up to 24 months. The primary outcome was the change in modified Rodnan skin score (mRSS). Confounding by indication at baseline was accounted for using inverse probability of treatment (IPT) weights. As a secondary outcome, an IPT-weighted Cox model was used to test for differences in survival. RESULTS: Of 326 patients recruited from 50 centres, 65 were prescribed methotrexate, 118 MMF, 87 cyclophosphamide and 56 no immunosuppressant. 276 (84.7%) patients completed 12 and 234 (71.7%) 24 months follow-up (or reached last visit date). There were statistically significant reductions in mRSS at 12 months in all groups: -4.0 (-5.2 to -2.7) units for methotrexate, -4.1 (-5.3 to -2.9) for MMF, -3.3 (-4.9 to -1.7) for cyclophosphamide and -2.2 (-4.0 to -0.3) for no immunosuppressant (p value for between-group differences=0.346). There were no statistically significant differences in survival between protocols before (p=0.389) or after weighting (p=0.440), but survival was poorest in the no immunosuppressant group (84.0%) at 24 months. CONCLUSIONS: These findings may support using immunosuppressants for early dcSSc but suggest that overall benefit is modest over 12 months and that better treatments are needed. TRIAL REGISTRATION NUMBER: NCT02339441.

Immunoglobulin A Vasculitis Complicated with Clostridium difficile Infection: a Rare Case Report and Brief Review of the Literature.

Immunoglobulin A (IgA) vasculitis, formerly called Henoch-Schönlein purpura, is a leukocytoclastic type of vasculitis affecting small vessels with a deposition of immune IgA complexes, clinically characterized by the classic tetrad of nonthrombocytopenic palpable purpura, arthralgia (or arthritis), and gastrointestinal and renal involvement. Although the cause of the disease remains unknown, immune complexes of IgA and unidentified antigens seem to play a central pathogenic role. The diagnosis is easily established in the presence of purpura, but may be challenging in its absence, especially when colicky abdominal pain precedes the cutaneous lesions. IgA vasculitis is usually a self-limited disease with a benign course and symptomatic treatment is sufficient for most; in severe cases, however, corticosteroids are necessary. We describe the case of a young adult male presenting with severe abdominal pain, vomiting and fever (38.4ºC). Clinical examination, abdominal ultrasound and plain abdominal radiography excluded an acute abdomen. The occurrence of arthralgia involving both knees and erosive duodenitis at endoscopy, 48 hours upon admission, suggested the diagnosis of IgA vasculitis, confirmed on the following day by the presence of typical purpuric rash on the lower extremities. Corticosteroid therapy led to the resolution of all gastrointestinal and joint manifestations as well as to a significant improvement of cutaneous purpura. However, during the 3rd week of corticosteroid treatment, the patient developed watery diarrhea and the clinical suspicion of Clostridium difficile infection (CDI) was confirmed. The treatment with metronidazole led to the resolution of diarrhea.The peculiarity of this case resides in several aspects: the gastrointestinal and joint manifestations preceded purpura, making diagnosis more difficult; CDI is an extremely rare complication of IgA vasculitis, being, in fact, the second case reported in adults in the literature.

An observational cohort study of patients with newly diagnosed digital ulcer disease secondary to systemic sclerosis registered in the EUSTAR database.

OBJECTIVES: This study describes clinical characteristics, prognostic factors, and quality of life in patients with newly diagnosed (incident) digital ulcers (DU). METHODS: Observational cohort study of 189 consecutive SSc patients with incident DU diagnosis identified from the EUSTAR database (22 centres in 10 countries). Data were collected from medical charts and during one prospective visit between 01/2004 and 09/2010. RESULTS: Median age at DU diagnosis was 51 years, majority of patients were female (88%), and limited cutaneous SSc was the most common subtype (61%). At incident DU diagnosis, 41% of patients had one DU and 59% had ≥2 DU; at the prospective visit 52% had DU. Pulmonary arterial hypertension (PAH) and multiple DU at diagnosis were associated with presence of any DU at the prospective visit (odds ratios: 4.34 and 1.32). During the observation period (median follow-up was 2 years) 127 patients had ≥1 hospitalisation. The event rate of new DU per person-year was 0.66, of DU-associated complications was 0.10, and of surgical or diagnostic procedures was 0.12. At the prospective visit, patients with ≥1 DU reported impairment in daily activities by 57%, those with 0 DU by 37%. The mean difference between patients with or without DU in the SF-36 physical component was 2.2, and in the mental component 1.4. DU patients were not routinely prescribed endothelin receptor antagonists or prostanoids. CONCLUSIONS: This real world cohort demonstrates that DU require hospital admission, and impair daily activity. PAH and multiple DU at diagnosis were associated with future occurrence of DU.

Rheumatoid myositis, myth or reality? A clinical, imaging and histological study.

UNLABELLED: Rheumatoid myositis (RM) is still poorly characterized, albeit the concept of muscle involvement in rheumatoid arthritis (RA) is well-recognized as being driven by a wide range of causes including inflammation, drugs, impaired joint flexibility, sedentarism. OBJECTIVE: To describe clinical, serological, imaging and histological pattern of RM. MATERIALS AND METHODS: This is a retrospective study on eight RM selected from a cohort of one hundred and three RA systematically assessed for skeletal muscle involvement. Data collected included clinical, serum muscle enzymes, muscle imaging and biopsy (Hematoxylin-Eosin, modified Gömöri trichrome staining). RESULTS: Routine muscle histology indicated both non-specific muscle fiber damage (changes in fiber size and internal structure: pleomorphic mitochondria, dilated sarcotubular system, multiple internal or subsarcommal nuclei; abnormal fiber types distribution: trend towards type II; atrophy; degenerative/regenerative modifications) and the presence of inflammatory deposits in all patients (mild to moderate, patchy B- and T-cells infiltrates, mainly perivascular and endomysial, but also in the perimysial region classified as polymyositis-like deposits). High levels of serum muscle enzymes, abnormal EMG (short duration, small amplitude, polyphasic motor unit action potentials) without insertional activity and fibrillations, active inflammation on both Doppler ultrasound and MRI were commonly reported. CONCLUSIONS: Traditional analysis of muscle biopsy specimens (Hematoxylin-Eosin, modified Gömöri trichrome staining) is faraway unsatisfactory, only documenting changes in muscle fibers size, architecture, internal structure, and, possibly, detecting perivascular, perimysial or endomysial inflammatory deposits. Upcoming research should address the value of muscle imaging for the diagnosis and evaluation of treatment response and muscle function in rheumatoid myositis.

Potential value of in situ cellular immune response in HPV subtype 16 and 18 positive cervical cancer.

UNLABELLED: There is no doubt that the association between infection of the cervical epithelium by carcinogenic Human Papilloma Virus (HPV), particularly types 16 and 18, and cervical cancer (CC) is responsible for the activation of the immune response (IR). Research on tumor infiltrating lymphocytes at the primary tumor site could give us important information on how the immune cells are fighting against cancer. AIM: The aims of our study were to assess HPV status and to evaluate the significance of in situ cellular IR in CC. MATERIALS AND METHODS: We performed a two-step retrospective analysis of IR in 18 CC: evaluation of HPV 16 and 18 infections by in situ hybridization and immune biomarkers (CD20, CD3, CD45) by immunohistochemistry. Immune cell profile, densities (assigned scores "0" if no inflammatory infiltrate, "1+" low, "2+" intense), tissue distribution and classical negative prognosis factors in relationship with survival and relapse were further assessed. RESULTS: We successfully demonstrated HPV 16 and/or 18 in all cases. We reported statistical significant correlations (p<0.005) between CD3, CD20, CD45 and survival (r=0.800), relapse (r=-0.892), clinical stage (r=-0.914), tumor size (r=-1) as well as the association between survival and CC subtype (r=0.548), FIGO stage (r=-0.914), tumor size (r=-0.800) and grading (r=0.61). CONCLUSIONS: The density of different immune cells is significantly involved in guiding prognosis of the CC in high-risk 16 and 18 HPV positive women; low cellular densities for CD3, CD20 and CD45 meaning limited immune response reflect negative disease outcomes promoting local relapse and decreased survival in such settings.

Thrombotic thrombocytopenic purpura: a hematological emergency.

UNLABELLED: Thrombotic thrombocytopenic purpura (TTP) is a rare but severe disease characterized by mechanical hemolytic anemia and consumptive thrombocytopenia leading to disseminated microvascular thrombosis that causes signs and symptoms of organ ischemia and functional damage. TTP is diagnosed by the presence of microangiopathic hemolytic anemia and thrombocytopenia in a patient who frequently presents with central nervous system involvement and, to a lesser extent, renal dysfunction. CASE REPORT: We present the case of a 23-year-old female with TTP, diagnosed by the presence of the neurological symptoms, microangiopathic hemolytic anemia and severe thrombocytopenia (platelets 4000/µL). During the clinical evolution, the patient presented the hepatic cytolysis syndrome, following disseminated microvascular thrombosis inside the liver, representing an atypical damage. The diagnosis was difficult because it was necessary to make differential diagnosis with other diseases that evolve with microangiopathic hemolytic anemia in a short time to be able to initiate plasmapheresis. Initiation of the plasmapheresis as soon as possible was the goal of our treatment. Following the plasmapheresis combined with administration of corticosteroids was achieved complete resolution of all symptoms. CONCLUSIONS: TTP is a hematological emergency and diagnostic challenge. The critical determinant of outcome is timely diagnosis and treatment. Once the diagnosis is suspected, life-saving therapeutic plasma exchange therapy is initiated.

Effects of Pilates, McKenzie and Heckscher training on disease activity, spinal motility and pulmonary function in patients with ankylosing spondylitis: a randomized controlled trial.

The optimal management of ankylosis spondylitis (AS) involves a combination of nonpharmacologic and pharmacologic treatment aiming to maximize health-related quality of life. The primary objective of our study was to demonstrate the benefits of an original multimodal exercise program combining Pilates, McKenzie and Heckscher techniques on pulmonary function in patients with AS, while secondary objectives were to demonstrate the benefits of the same program on function and disease activity. This is a randomized controlled study on ninety-six consecutive patients with AS (axial disease subset), assigned on a 1:1 rationale into two groups based on their participation in the Pilates, McKenzie and Heckscher (group I) or in the classical kinetic program (group II). The exercise program consisted of 50-min sessions performed 3 times weekly for 48 weeks. Standard assessments were done at week 0 and 48 and included pain, modified Schober test (mST) and finger-floor distance (FFD), chest expansion (CE) and vital capacity (VC), as well as disease activity Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), functional Bath Ankylosing Spondylitis Functional Index (BASFI) and metrology index Bath Ankylosing Spondylitis Metrology Index (BASMI). Groups were comparable at baseline; we demonstrated significant improvement between baseline and after 48 weeks of regular kinetic training for all AS-related parameters in both groups. However, significant improvement was found in pain, lumbar spine motility (mST, FFD), BASFI, BASDAI and BASMI in AS performing the specific multimodal exercise program at the end of study (p = 0.001). Although there were significant improvements in CE in both groups as compared to baseline (group I, p = 0.001; group II, p = 0.002), this parameter increased significantly only in group I (p = 0.001). VC measurements were not significantly changed at the end of the study (group I, p = 0.127; group II, p = 0.997), but we found significant differences within groups (p = 0.011). A multimodal training combining Pilates, McKenzie and Heckscher exercises performed regularly should be included in the routine management of patients with AS for better control of function, disease activity and pulmonary function.

Lichen planus secondary complications associated with the use of biologic therapy for rheumatoid arthritis.

OBJECTIVES: Biologic therapy such as Etanercept, which is a tumor necrosis factor alpha (TNF-α) inhibitor, has been extensively used as election therapy in rheumatoid arthritis. The purpose of this case presentation was to inform about the possibility that lichen planus lesions could potentially become complicated by secondary infections in patients treated with Etanercept. Furthermore, we aimed at analyzing if the complication of the cutaneous lesion was coincidental or it was due to the immunosuppressive systemic therapy, and whether the infected lesion would respond to antibiotic therapy. CASE SUMMARY: The patient was a 59-year-old woman with rheumatoid arthritis and that have had lichen planus lesions for approximately 25 years. Only recently, she had been received immunosuppressive therapy (Etanercept and Methotrexate). Further on, the lichen planus flared up with a secondary infection determined by a Methicillin-sensitive Staphylococcus aureus. Uncommon myocardial complications were also characteristic of this case. RESULTS: While a case report described already the appearance of lichen planus following Etanercept therapy (Battistella M et al., 2008), the possibility that the lesion could become secondary complicated following this therapy was never reported before, according to our knowledge. Additionally, we describe in this case the interplay between Etanercept therapy and hypertrophic cardiomyopathy. CONCLUSIONS: Our case is not a lichen planus induced by Etanercept, but it is aggravated and secondary infected with Methicillin-sensitive Staphylococcus during the therapy. The additional cardiac complication (hypertrophic cardiomyopathy) may represent solely an evolutive sign of rheumatoid arthritis and therefore not influenced by Etanercept.

A predictive model for remission and low disease activity in patients with established rheumatoid arthritis receiving TNF blockers.

The objective of this study was to identify predictors for remission or low disease activity (LDA) in established rheumatoid arthritis (RA) at 12 months of anti-TNF-α therapy. We have performed a prospective observational study in 90 consecutive patients with active RA receiving TNF-α inhibitors. Baseline and standard assessments were done every 3 months, including individual parameters (clinical and biological) and composite activity scores (28-joint disease activity score, DAS28). The primary outcome measure was DAS28-based EULAR response criteria. The multivariate logistic regression was used to analyze the association between disease activity and several RA baseline characteristics. Of the RA, 78.8 % was classified as good responders based on the EULAR-DAS28 criteria, 44.4 % RA achieving remission (DAS28 ≤ 2.6) and 34.4 %, LDA (DAS28 ≤ 3.2). Parameters associated with an increased likelihood of remission and LDA were initial DAS28-erythrocyte sedimentation rate ≤ 7 (odds ratio (OR) 3.3, 95 % confidence interval (CI) 2.03-5.81; OR 1.8, 95 % CI 1.09-6.68), Health Assessment Questionnaire Disability Index ≤ 2 (OR 7.0, 95 % CI 1.56-31.91; OR 1.3, 95 % CI 1.03-5.79), C-reactive protein level ≤ 20 mg/l (OR 1.5, 95 % CI 0.29-8.22; OR 0.5, 95 % CI0.08-2.97), rheumatoid factor ≤ 20 IU/ml (OR 18.9, 95 % CI 10.79-38.36; OR 32.9, 95 % CI 4.03-269), anti-cyclic citrullinated peptide antibodies ≤ 40 IU/ml (OR 3.5, 95 % CI 0.67-18.19; OR 1.2, 95 % CI 1.02-1.59), concurrent prednisolone (OR 0.2, 95 % CI 0.05-0.36; OR 0.2, 95 % CI 0.06-0.63), methotrexate or leflunomide (OR 1.6, 95 % CI 1.2-13.53; OR 2.9, 95 % CI 1.20-4.36). A predictive matrix for remission and LDA in established active RA patients receiving TNF-α inhibitors was proposed. Further studies are necessary to confirm the value of such matrix in particular RA settings, leading to optimization of the use of anti-TNF-α therapy.

Comparison of two referral strategies for diagnosis of axial spondyloarthritis: the Recognising and Diagnosing Ankylosing Spondylitis Reliably (RADAR) study.

OBJECTIVE: To determine which of two referral strategies, when used by referring physicians for patients with chronic back pain (CBP), is superior for diagnosing axial spondyloarthritis (SpA) by rheumatologists across several countries. METHODS: Primary care referral sites in 16 countries were randomised (1 : 1) to refer patients with CBP lasting >3 months and onset before age 45 years to a rheumatologist using either strategy 1 (any of inflammatory back pain (IBP), HLA-B27 or sacroiliitis on imaging) or strategy 2 (two of the following: IBP, HLA-B27, sacroiliitis, family history of axial SpA, good response to non-steroidal anti-inflammatory drugs, extra-articular manifestations). The rheumatologist established the diagnosis. The primary analysis compared the proportion of patients diagnosed with definite axial SpA by referral strategy. RESULTS: Patients (N=1072) were referred by 278 sites to 64 rheumatologists: 504 patients by strategy 1 and 568 patients by strategy 2. Axial SpA was diagnosed in 35.6% and 39.8% of patients referred by these respective strategies (between-group difference 4.40%; 95% CI -7.09% to 15.89%; p=0.447). IBP was the most frequently used referral criterion (94.7% of cases), showing high concordance (85.4%) with rheumatologists' assessments, and having sensitivity and a negative predictive value of >85% but a positive predictive value and specificity of <50%. Combining IBP with other criteria (eg, sacroiliitis, HLA-B27) increased the likelihood for diagnosing axial SpA. CONCLUSIONS: A referral strategy based on three criteria leads to a diagnosis of axial SpA in approximately 35% of patients with CBP and is applicable across countries and geographical locales with presumably different levels of expertise in axial SpA.