Patient reported outcome for physical function in idiopathic inflammatory myopathy.

OBJECTIVES: There is an unmet need to develop patient-reported outcomes (PRO) measures for Idiopathic Inflammatory Myopathies (IIM). To investigate the feasibility, compliance, and psychometric properties of NIH's Patient-Reported Outcomes Measurement Information System (PROMIS) physical function-20 (PF-20) in a large U.S. IIM population. METHODS: "Myositis Patient Centered Tele-Research" (My PACER) is a multicentre prospective observational study of IIM patients, competitively recruited through traditional in-person clinic visits (Center-Based Cohort [CBC]), and remotely using smartphone and web-based technology (Tele-Research Cohort [TRC]). The CBC was further randomly divided (1:1 ratio) into a traditional local sub-cohort, and a remote sub-cohort. Data collected included PRO and other patient self-assessments monthly for 6 months. Clinician-reported outcomes were obtained at baseline and 6 months. RESULTS: 120 IIM patients were enrolled (82 TRC/38 CBC, mean age 55 ± 13.4, 75% females, 81% Caucasians), with similar demographics and mean PROMIS PF-20 score between cohorts. The PROMIS PF-20 score was not associated with age, sex or race. The compliance and completion rates were similar between TRC and CBC as well as sub-cohorts. PROMIS PF-20 showed strong test-retest reliability at 1 month. PROMIS PF-20 was significantly associated with all core set measures except extra-muscular global and CK, as well as with most of symptoms, function and physical activity measures. PROMIS PF-20 illustrated concordant change with myositis response criteria and patient assessment, with a large effect size. CONCLUSIONS: PROMIS PF-20 demonstrates favorable psychometric properties including reliability, validity and responsiveness in a large cohort of myositis patients, with similar adherence in local or remotely enrolled patients.

Pain is Common in Myositis and Associated with Disease Activity.

BACKGROUND: Understanding pain in myositis remains challenging. This study aimed to assess patient-reported pain and its correlation with myositis core set measures (CSMs), patient-reported outcomes (PROs), and functional measures. METHODS: Fifty subjects underwent baseline, 3-month, and 6-month assessments, evaluating myositis CSMs, functional measures, and patient-reported outcomes. Pain was measured using three methods: (1) a 10-cm Visual Analogue Scale (VAS), (2) pain score from the HAQ-DI, and (3) SF-36 (Short Form survey) pain questions. Correlations between disease activity measures and pain were examined at baseline, and changes in both were assessed at 6 months, along with longitudinal change of pain. The change in pain was also correlated with the published 2016 ACR/EULAR myositis response criteria, physician/patient's assessment of change. RESULTS: Nearly half of patients (45%) reported moderate to severe pain in all 3 pain scales, with higher severity of pain in PM/NM subset. At baseline, pain severity showed a strong correlation with most CSMs, PROs and functional outcomes in all the 3 pain scales and similar trends were noted for change in pain at the 6 months. On longitudinal analysis, the physical function scores and fatigue showed strong correlation with pain. Pain improved in myositis patients with improvement in disease activity over time. CONCLUSIONS: Pain is common in myositis and is associated with multiple measures of disease activity, PROs, and functional outcomes in myositis. Most importantly pain improves with improvement in disease activity. SF-36 pain questions have good psychometric properties.

Discordance between patient- and physician-reported disease activity in adult idiopathic inflammatory myopathy.

OBJECTIVES: Patient-reported global disease activity (patient-global) is a myositis core set measure. Understanding the drivers of patient-global is important in patient assessment, and disagreements between physician and patient perception of disease activity may negatively impact shared decision making. We examined the determinants of patient-global and discordance between patient-global and physician-reported global disease activity (physician-global) in idiopathic inflammatory myopathies (IIMs). METHODS: Adults with IIM were enrolled in a prospective observational cross-sectional study. The following myositis outcome measures were collected: patient-global, physician-global, extramuscular and muscle disease activity, manual muscle testing, HAQ, creatine kinase, fatigue, pain, Patient-Reported Outcomes Measurement Information System physical function, 36-item Short Form, sit to stand, timed up and go, 6-minute walk and Actigraph steps/min/day count. A linear regression model was used to determine the contribution of each measure to patient-global. Discordance was defined as ≥3 points difference between patient-global and physician-global. RESULTS: Fifty patients [60% females; mean age 51.6 years (s.d. 14.9)] with probable/definite IIM (EULAR/ACR classification criteria for IIM) were enrolled. Physical function and fatigue measures contributed to patient-global the most, followed by measures of pain, physical activity, quality of life and muscle disease, while physician-global was primarily driven by muscle disease activity. Patient-global was discordant with physician-global in 30% of the patients, of which patient-global was higher than physician-global in 66%. Pain, fatigue and physical activity contributed more to patient-global than physician-global. CONCLUSION: Fatigue, pain and physical activity are important driving factors of the differences observed in the patient vs physician assessment of myositis disease activity. Understanding the gap between patient and physician perspectives may help provide better patient-centred care.

Outcomes in progressive systemic sclerosis treated with autologous hematopoietic stem cell transplantation compared with combination therapy.

OBJECTIVES: Autologous hematopoietic stem cell transplantation (AHSCT) has been shown to improve long-term survival for early diffuse progressive systemic sclerosis (SSc) compared with cyclophosphamide. Cyclophosphamide, however, does not provide a long-term benefit in SSc. The combination of mycophenolate mofetil (MMF) and rituximab is a potent alternative regimen. We aimed to retrospectively compare the outcomes of SSc patients who underwent AHSCT to patients who met the eligibility criteria for AHSCT but received upfront combination therapy with MMF and rituximab. METHODS: Repeated assessments of modified Rodnan Skin Score (mRSS), forced vital capacity (FVC), and diffusing capacity (DLCO) values were conducted. Clinical improvement was defined as an mRSS decrease > 25% or an FVC increase > 10%. Event-free survival (EFS) was defined in the absence of persistent major organ failure or death. RESULTS: Twenty-one SSc patients in the combination therapy group were compared with sixteen in the AHSCT group. Age, sex and disease duration were similar between the two groups. Clinical improvement at 12 months was seen in 18 (86%) patients in the combination group compared with 13 (81%) in the AHSCT group (p= 0.7). The hazard ratio for EFS at 24 months favored the combination group (HR = 0.09, P= 0.04). During follow-up, both groups exhibited a significant and comparable reduction in mRSS and an increase in FVC values at each time interval up to 24 months. CONCLUSION: MMF and rituximab compared with AHSCT in SSc patients eligible for AHSCT resulted in similar skin and lung clinical improvement with a better safety profile at 24 months.

Nailfold video capillaroscopy as a useful diagnostic tool in systemic vasculitis.

BACKGROUND: Nailfold video capillaroscopy (NVC) enables us a direct view of the microvasculature. Only several capillaroscopy studies in adult patients with vasculitis have been reported. AIM: To characterize NVC changes in vasculitis. METHODS: Vasculitis patients and healthy controls were evaluated by NVC. NVC changes associated with vasculitis were assessed retrospectively in a cohort of 100 patients with Raynaud's phenomenon (RP). RESULTS: 17 patients with active vasculitis and 8 patients with vasculitis in remission were compared to 25 age and sex-matched healthy controls. Active vasculitis patients demonstrated higher rates of neoangiogenesis and capillary loss in comparison to other groups. Two novel NVC abnormalities were observed in patients with vasculitis: "Rolling" (slow capillary flow) and "peri-capillary stippling" (PCS), small deposits that may represent capillary leak. PCS was observed exclusively in 5 of 17 patients with active vasculitis. Retrospectively, we were able to detect PCS also in 14 % of 100 patients that were evaluated for RP, of whom 64 % were diagnosed with scleroderma or a related disorder. CONCLUSIONS: Patients with active vasculitis demonstrate frequent capillary abnormalities. Although these abnormalities are non-specific, we suggest that their combination may aid the diagnosis of vasculitis. Future studies are needed to validate our findings.

Costovertebral joint involvement in radiographic axial spondyloarthritis: A case-series computed tomography study.

AIMS: To evaluate structural changes of costovertebral joints (CVJ) in patients with radiographic axial spondyloarthritis (rAxSpA) using computed tomography (CT) studies. METHODS: Available chest or thoracic spine CT studies of 17 patients with rAxSpA and 17 patients with rheumatoid arthritis (RA) were analyzed. Ankylosis, erosions, joint space narrowing, and osteophytes were assessed. RESULTS: The groups were similar by patients' average age, but the rAxSpA group included more males (11/17) compared to the RA group (4/17, p = 0.036). In all, 748 CVJ were assessed in each patient group, including 408 head-vertebral joints (HVJ) and 340 costotransverse joints (CTJ). rAxSpA patients had significantly more total CVJ lesions (p < 0.001 for all comparisons), more lesions in the HVJ (p < 0.001, for all comparisons), and more lesions in the CTJ (p ≤ 0.005, for all comparisons, except for osteophytes), compared to the RA group. All types of lesions, including ankylosis, erosions, narrowing, and osteophytes, were seen more frequently in rAxSpA patients. Joint space narrowing and ankylosis of the CVJ were the most frequently seen findings in rAxSpA and were distributed throughout the thoracic spine. CONCLUSIONS: Structural pathology of the CVJ was more commonly observed in patients with rAxSpA than in RA patients in this study.

Facet joint involvement in the inflammatory rheumatic disease.

BACKGROUND: The involvement of facet joints (FJ) in patients with inflammatory rheumatic disorders remains underexplored. This review aims to look at FJ disease from a rheumatologist's perspective, with the emphasis given to the clinical presentations and patterns of FJ engagement in axial spondyloarthritis (axSpA), psoriatic arthritis (PsA), rheumatoid arthritis (RA), and crystal-related arthropathies, and discussion of challenges in studying FJ in rheumatic disease. METHODS: A systematic PubMed search using the pertinent keywords was performed, relevant articles extracted, and the acquired data critically assessed, interpreted, and organized according to the authors' experience and judgment. RESULTS: FJ involvement is common in patients with radiographic axSpA, occurs throughout the spine, but is more frequently seen in the thoracic segment. The existing data suggests that the FJ are primarily affected by the disease process, while altered spine biomechanics due to the presence of syndesmophytes at the same vertebral level contributes to the FJ fusion. Predominant involvement of FJ of the cervical spinal segment has been suggested in PsA; however, prevalence and clinical significance of FJ involvement in PsA is still markedly underexplored. RA-related FJ disease of the cervical spine in patients with poorly controlled RA is not uncommon and can be related to significant morbidity, while the burden of FJ involvement in the thoracic and lumbar spinal segments in RA is also underexplored. FJ disease is possible in the course of crystal-related arthropathies, but the high level of suspicion is a prerequisite for the timely diagnosis. CONCLUSIONS: The involvement of FJ in the course of inflammatory rheumatic disease is not uncommon. Prospective studies are needed to understand the epidemiology and significance of FJ disease in inflammatory rheumatic conditions.

Differentially expressed genes in systemic sclerosis: Towards predictive medicine with new molecular tools for clinicians.

Systemic sclerosis (SSc) is a rare and chronic autoimmune disease characterized by a pathogenic triad of immune dysregulation, vasculopathy, and progressive fibrosis. Clinical tools commonly used to assess patients, including the modified Rodnan skin score, difference between limited or diffuse forms of skin involvement, presence of lung, heart or kidney involvement, or of various autoantibodies, are important prognostic factors, but still fail to reflect the large heterogeneity of the disease. SSc treatment options are diverse, ranging from conventional drugs to autologous hematopoietic stem cell transplantation, and predicting response is challenging. Genome-wide technologies, such as high throughput microarray analyses and RNA sequencing, allow accurate, unbiased, and broad assessment of alterations in expression levels of multiple genes. In recent years, many studies have shown robust changes in the gene expression profiles of SSc patients compared to healthy controls, mainly in skin tissues and peripheral blood cells. The objective analysis of molecular patterns in SSc is a powerful tool that can further classify SSc patients with similar clinical phenotypes and help predict response to therapy. In this review, we describe the journey from the first discovery of differentially expressed genes to the identification of enriched pathways and intrinsic subsets identified in SSc, using machine learning algorithms. Finally, we discuss the use of these new tools to predict the efficacy of various treatments, including stem cell transplantation. We suggest that the use of RNA gene expression-based classifications according to molecular subsets may bring us one step closer to precision medicine in Systemic Sclerosis.

Osteopontin Upregulation, Induced by the Continuous Mechanical Load in Adipose Tissue-Derived Mesenchymal Stem Cells, is Strongly Restricted in INF-γ/TNF-α/IL-22 Microenvironment.

The osteogenic potential of mesenchymal stem cells (MSc) in axial spondyloarthritis (AxSpA) depends on the interplay of inflammation and multiple hormonal and local mechanical factors. In this study, MCs, derived from the adipose tissue of a healthy donor, were cultured under or without continuous mechanical load in the osteogenic differentiation medium with or without the addition of testosterone, cocktail of INF-γ/TNF-α/IL-22, or both. Real-time PCR for osteogenic transcription factors demonstrated that in the absence of INF-γ/TNF-α/IL-22, mechanical load causes significant upregulation of SPP1 (osteopontin), while the presence of the inflammatory cytokines almost completely abolishes this effect. In addition, exposure to INF-γ/TNF-α/IL-22 slightly upregulated BMP2, but suppressed the expression of ALPL, Col1A1, and SPP1, reinforcing the hypothesis that the inflammatory environment allows MSc to commit toward the IL-22-driven osteogenic differentiation but can restrict the later stages of osteogenesis. In summary, osteopontin can play a role in the pathogenesis of AxSpA, linking between mechanical load and pathological bone formation.

Giant Cell Arteritis: State of the Art in Diagnosis, Monitoring, and Treatment.

Giant cell arteritis (GCA) is the most prevalent subtype of vasculitis in adults. In recent years, there has been substantial improvement in the diagnosis and treatment of GCA, mainly attributed to the introduction of highly sensitive diagnostic tools, incorporation of modern imaging modalities for diagnosis and monitoring of large-vessel vasculitis, and introduction of highly effective novel biological therapies that have revolutionized the field of GCA. This article reviews state-of-the-art approaches for the diagnosis, monitoring, and treatment options of GCA.

Approach to a patient with monoarticular disease.

PURPOSE: To reassess the diagnostic approach to a patient with a monoarticular disease in light of the up-to-date medical literature and to examine the practical utility of traditional and newer imaging tools in the setting of monoarthritis. RESULTS: The monoarticular disease can represent a medical emergency on the one hand and be a diagnostic conundrum on the other. The management rules of patients with monoarthritis have been established long ago, but various pitfalls still lead physicians off the right diagnosis at times. Septic, pseudoseptic arthritis and hemarthrosis are the most common diagnoses made in patients with an acute presentation, and a decision not to perform a diagnostic arthrocentesis is the most prevalent cause of misdiagnosis in this setting. Many rheumatic and infectious diseases can present with more indolent monoarthritis; careful history and physical examination frequently provide clues to the straightforward diagnosis in some cases, but the extensive investigation is needed in others. Imaging methods become indispensable in individuals with the non-inflammatory monoarticular disease, with magnetic resonance imaging being the gold standard for diagnosing pigmented villonodular synovitis, lipoma arborescence, avascular necrosis, or neuropathic arthropathy. CONCLUSIONS: A great variety of medical disorders can present as a monoarticular disease. The disease presentation dictates different diagnostic behavior, while knowing the available imaging methods' diagnostic potential should further shorten the diagnostic process.