In inflammatory myopathies, dropped head/bent spine syndrome is associated with scleromyositis: an international case-control study.

BACKGROUND: Some myopathies can lead to dropped head or bent spine syndrome (DH/BS). The significance of this symptom has not been studied in inflammatory myopathies (IM). OBJECTIVES: To assess the significance of DH/BS in patients with IM. METHODS: Practitioners from five IM networks were invited to report patients with IM suffering from DH/BS (without other known cause than IM). IM patients without DH/BS, randomly selected in each participating centre, were included as controls at a ratio of 2 to 1. RESULTS: 49 DH/BS-IM patients (DH: 57.1%, BS: 42.9%) were compared with 98 control-IM patients. DH/BS-IM patients were older (65 years vs 53 years, p<0.0001) and the diagnosis of IM was delayed (6 months vs 3 months, p=0.009). Weakness prevailing in the upper limbs (42.9% vs 15.3%), dysphagia (57.1% vs 25.5%), muscle atrophy (65.3% vs 34.7%), weight loss (61.2% vs 23.5%) and loss of the ability to walk (24.5% vs 5.1%) were hallmarks of DH/BS-IM (p≤0.0005), for which the patients more frequently received intravenous immunoglobulins (65.3% vs 34.7%, p=0.0004). Moreover, DH/BS-IM patients frequently featured signs and/or complications of systemic sclerosis (SSc), fulfilling the American College of Rheumatology/European Alliance of Associations for Rheumatology criteria for this disease in 40.8% of the cases (vs 5.1%, p<0.0001). Distribution of the myopathy, its severity and its association with SSc were independently associated with DH/BS (p<0.05). Mortality was higher in the DH/BS-IM patients and loss of walking ability was independently associated with survival (p<0.05). CONCLUSION: In IM patients, DH/BS is a marker of severity and is associated with SSc (scleromyositis).

Strategy and Challenges of Paraclinical Examinations in Adult-Onset Still's Disease.

Adult-onset Still's disease is a complex autoinflammatory disease with a multifactorial etiology. Its presentation is less stereotypical than that of a monogenic autoinflammatory disease and is actually relatively common with few specific signs. To avoid under- or over-prescription of complementary examinations, it is useful to advance in a structured manner, taking into consideration the actual added value of each supplemental examination. In this review, we detail the different complementary tests used in adult Still's disease. We consider them from three different angles: positive diagnostic approach, the differential diagnosis, and the screening for complications of the disease. After discussing the various tests at our disposal, we look at the classical diagnostic strategy in order to propose a structured algorithm that can be used in clinical practice. We conclude with the prospects of new complementary examinations, which could in the future modify the management of patients.

Granulomatosis-associated myositis: High prevalence of sporadic inclusion body myositis.

OBJECTIVE: To refine the predictive significance of muscle granuloma in patients with myositis. METHODS: A group of 23 patients with myositis and granuloma on muscle biopsy (granuloma-myositis) from 8 French and Belgian centers was analyzed and compared with (1) a group of 23 patients with myositis without identified granuloma (control-myositis) randomly sampled in each center and (2) a group of 20 patients with sporadic inclusion body myositis (sIBM) without identified granuloma (control-sIBM). RESULTS: All but 2 patients with granuloma-myositis had extramuscular involvement, including signs common in sarcoidosis that were systematically absent in the control-myositis and the control-sIBM groups. Almost half of patients with granuloma-myositis matched the diagnostic criteria for sIBM. In these patients, other than the granuloma, the characteristics of the myopathy and its nonresponse to treatment were similar to the control-sIBM patients. Aside from 1 patient with myositis overlapping with systemic sclerosis, the remaining patients with granuloma-myositis did not match the criteria for a well-defined myositis subtype, suggesting pure sarcoidosis. Matching criteria for sIBM was the sole feature independently associated with nonresponse to myopathy treatment in patients with granuloma-myositis. CONCLUSION: Patients with granuloma-myositis should be carefully screened for sIBM associated with sarcoidosis in order to best tailor their care.

Impact of systemic sclerosis oral manifestations on patients' health-related quality of life: A systematic review.

BACKGROUND: Oropharyngeal features are frequent and often understated in the treatment clinical guidelines of systemic sclerosis in spite of important consequences on comfort, aesthetics, nutrition and daily life. The aim of this systematic review was to assess a correlation between the oropharyngeal manifestations of systemic sclerosis and patients' health-related quality of life. METHODS: A systematic search was conducted using four databases [PubMed® , Cochrane Database® , Dentistry & Oral Sciences Source® and SCOPUS® ] up to January 2018, according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses. Grey literature and hand search were also included. Study selection, risk bias assessment (Newcastle-Ottawa scale) and data extraction were performed by two independent reviewers. The review protocol was registered on PROSPERO database with the code CRD42018085994. RESULTS: From 375 screened studies, 6 cross-sectional studies were included in the systematic review. The total number of patients included per study ranged from 84 to 178. These studies reported a statistically significant association between oropharyngeal manifestations of systemic sclerosis (mainly assessed by maximal mouth opening and the Mouth Handicap in Systemic Sclerosis Scale) and an impaired quality of life (measured by different scales). Studies were unequal concerning risk of bias mostly because of low level of evidence, different recruiting sources of samples and different scales to assess the quality of life. CONCLUSION: This systematic review demonstrates a correlation between oropharyngeal manifestations of systemic sclerosis and impaired quality of life, despite the low level of evidence of included studies. Large-scaled studies are needed to provide stronger evidence of this association.

Ultrasonography and detection of subclinical joints and tendons involvements in Systemic Lupus erythematosus (SLE) patients: A cross-sectional multicenter study.

OBJECTIVES: The aims of this study in SLE population were (1) to describe ultrasonography (US) joint abnormalities, (2) to estimate the reliability of clinical swollen joint count (C-SJC) and SLEDAI (C-SLEDAI) versus US-SJC and US-SLEDAI scores, (3) to highlight specific patterns of lupus patients with Power Doppler (PD) abnormalities. METHOD: For this cross-sectional multicenter study, 151 consecutive adult SLE patients were recruited. Evaluation included a clinical standardized joint assessment, B-mode and PD US of 40 joints and 26 tendons blinded for clinical examination. Reliability and agreement between clinical and B-mode US were calculated using the intraclass correlation coefficients (ICC [95% Confidence Interval]). RESULTS: We found a very high frequency of subclinical US abnormalities in asymptomatic patients: 85% of patients without joint symptoms had at least 1 US abnormality. Among them 46 patients (87%) had a history of joint involvement. The most frequent abnormalities were joint effusmaions (108 patients), synovial hypertrophy (SH, 109 patients) and synovitis (61 patients). Joint or tendon PD signal (grade>1) was found in 44% of patients (67/151). Synovitis were mainly located especially on MCPs and wrists. Even if reliability between clinical and grey-scale US SJC assessments was poor, reliability between clinical and US SLEDAI was good. Comparison between SLE patients with and without PD signal did not show any specific SLE pattern. CONCLUSION: US may be useful to assess joint involvement in SLE patients but did not significantly change SLEDAI score.

Orofacial consequences of systemic sclerosis: A systematic review.

Orofacial involvement is common and often understated in the treatment clinical guidelines of systemic sclerosis. It impairs daily life by having repercussions on comfort, nutrition, aesthetics and self-confidence. This review aimed at describing exhaustively the different orofacial consequences of systemic sclerosis. A systematic search was conducted using four databases (PubMed, Cochrane Library, Dentistry & Oral Sciences Source and SCOPUS) up to December 2016 according to the Preferred Reporting Items for Systematic Reviews and Meta-analyses. Grey literature and hand search were also included. To be eligible for the inclusion, studies needed to meet the following criteria: randomised controlled trials, cross-sectional studies, case-control studies, pilot studies or cohort studies and full text available in English or French, with abstract. The studies had to concern at least 30 patients suffering from systemic sclerosis and having clinical and radiological oropharyngeal examination. The diagnosis of systemic sclerosis had to be determined according to precise recommendations; the retrieved oropharyngeal manifestations had to affect hard or soft tissues of the mouth and/or pharynx and needed to be evaluated with clinical measures. Study selection, risk bias assessment (Newcastle-Ottawa scale) and data extraction were performed by two independent reviewers. The retrieved features were microstomia and xerostomia associated with real hyposialia, temporomandibular joint symptoms, high caries experience, periodontal diseases as well as an increased risk of oral cavity and pharynx cancer. Early diagnosis enabling early management, prevention and oral hygiene is the key to avoid complicated and invasive procedures. Studies with higher level of evidence remain necessary to create standardised protocols.

Multireader assessment as an alternative to reference assessment to improve the detection of radiographic progression in a large longitudinal cohort of rheumatoid arthritis (ESPOIR).

INTRODUCTION: Structural damage progression is a major outcome in rheumatoid arthritis (RA). Its evaluation and follow-up in trials should involve radiographic scoring by 1 or 2 readers (reference assessment), which is challenging in large longitudinal cohorts with multiple assessments. OBJECTIVES: To compare the reproducibility of multireader and reference assessment to improve the feasibility of detecting radiographic progression in a large cohort of patients with early arthritis (ESPOIR). METHODS: We used 3 sessions to train 12 rheumatologists in radiographic scoring by the van der Heijde-modified Sharp score (SHS). Multireader scoring was based on 10 trained-reader assessments, each reader scoring a random sample of 1/5 of all available radiographs (for double scoring for each X-ray set) for patients included in the ESPOIR cohort with complete radiographic data at M0 and M60. Reference scoring was performed by 2 experienced readers. Scoring was performed blindly to clinical data, with radiographs in chronological order. We compared multireader and reference assessments by intraclass correlation coefficients (ICCs) for SHS and significant radiographic progression (SRP). RESULTS: The intrareader and inter-reader reproducibility for trained assessors increased during the training sessions (ICC 0.79 to 0.94 and 0.76 to 0.92), respectively. For the 524 patients included, agreement between multireader and reference assessment of SHS progression between M0 and M60 and SRP assessment were almost perfect, ICC (0.88 (95% CI 0.82 to 0.93)) and (0.99 (95% CI 0.99 to 0.99)), respectively. CONCLUSIONS: Multireader assessment of radiographic structural damage progression is comparable to reference assessment and could be used to improve the feasibility of radiographic scoring in large longitudinal cohort with numerous X-ray evaluations.

Abatacept monotherapy compared with abatacept plus disease-modifying anti-rheumatic drugs in rheumatoid arthritis patients: data from the ORA registry.

BACKGROUND: Retention rate, efficacy, and safety of abatacept (ABA) was compared between patients with rheumatoid arthritis receiving ABA as monotherapy to those in combination ABA + conventional synthetic DMARD (csDMARD). METHODS: The patients were obtained from the ORA registry. The retention rate was analysed in two ways: (1) therapeutic strategy retention, in which the addition of a csDMARD was considered to indicate failure of the monotherapy strategy; and (2) ABA retention, which was assessed by the discontinuation of ABA regardless of other treatment modifications. Efficacy and safety were compared between ABA initiated alone and ABA used in combination with a csDMARD. RESULTS: The retention rate at month 6 (M6) was evaluated in 569 patients. A significant difference was identified in the retention rate between the ABA monotherapy strategy and the ABA + csDMARD strategy (58.5 % [110/188] vs. 68 % [258/381], respectively, p = 0.031). No significant difference was identified in the ABA retention rate initiated either as a monotherapy or in combination with csDMARDs (75 % [142/188] vs. 76 % [291/381], respectively, p = 0.824). Data regarding ABA efficacy were available for 444 patients. There was no significant difference in the responder proportion after 6 months of treatment between ABA monotherapy and ABA + csDMARD treatment (60.2 % [88/146] vs. 60 % [179/298], respectively, p = 0.967). CONCLUSIONS: This "real-life" analysis, which is relevant for bedside practice, emphasised the satisfactory efficacy and safety of ABA used in monotherapy, which provides an acceptable alternative when csDMARDs are undesirable.

A pharmacokinetic and clinical assessment of tofacitinib for the treatment of rheumatoid arthritis.

INTRODUCTION: Rheumatoid arthritis (RA) is a chronic painful and debilitating autoimmune disease. Although the outcome for patients with RA has improved markedly in the past decades, driven largely by the advent of biological disease-modifying antirheumatic drugs (DMARDs) and updated management strategies, adequate disease control cannot be achieved in a substantial proportion of patients. Since RA is a syndrome with different biological subsets, DMARDs, with a novel mechanism of action, may represent a valuable addition to the current armamentarium. Tofacitinib is a novel synthetic DMARD that selectively inhibits Janus kinases (JAKs), particularly JAK1 and JAK3. AREAS COVERED: This review describes the pharmacokinetics of tofacitinib. Furthermore, the article summarizes and comments the drug's efficacy and safety profile in RA patients. The authors furthermore assess data derived from the FDA's RA development program. EXPERT OPINION: Tofacitinib is an oral synthetic DMARD displaying linear pharmacokinetics. Metabolism, primarily mediated by CYP3A4, accounts for 70% of the total clearance of the drug; the remaining 30% are renally excreted. Tofacitinib monotherapy, or in combination with traditional DMARDs, has demonstrated its efficacy while having an acceptable safety profile in RA patients who have responded inadequately to current DMARDs, including TNF antagonists. In view of its undetermined benefit to risk ratio, in the real-world population, tofacitinib should, for now, only be prescribed to selected patients.