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.

Real-world effectiveness of tofacitinib in patients with rheumatoid arthritis: a prospective observational study.

OBJECTIVES: Tofacitinib is an approved treatment for rheumatoid arthritis (RA), but data on its use in the "real-world" are limited. We sought to analyse tofacitinib drug survival in the Israeli registry and compare it to other biologic agents. METHODS: We included RA patients treated with tofacitinib, etanercept, golimumab, tocilizumab, or abatacept between 2010-2019. The primary endpoint was event-free survival (EFS), defined as the time from treatment initiation to a treatment failure event from any cause (i.e., inefficacy or intolerability). EFS was compared between agents using Cox regression and Kaplan-Meier analysis, stratifying patients by treatment line. RESULTS: A total of 964 eligible treatment courses were included (tocilizumab [325], etanercept [284], abatacept [127], tofacitinib [139], and golimumab [109]). In a univariate analysis, EFS with tofacitinib in the complete cohort was similar to etanercept, golimumab, and abatacept but was lower than tocilizumab) 3-year EFS 43% vs. 53%, HR 0.65). In a multivariable analysis, tofacitinib was similar to all other drugs, except for etanercept, which was inferior (HR 1.70); advanced treatment line was also associated with greater risk for failure (HR 1.64). In a univariable analysis stratified by the treatment line, tofacitinib had similar or better drug survival than other agents in the first and second lines. In the third line and beyond, tocilizumab had a higher EFS compared to tofacitinib (HR 0.57). CONLUSIONS: Drug survival with tofacitinib is related to treatment line. Early introduction is associated with similar or better survival than other agents, whereas tocilizumab was superior in the third line or later.

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.

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.

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.

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.

Facet joint disease in patients with axial spondyloarthritis: A retrospective computed tomography study.

BACKGROUND: Facet joints' (FJ) ankylosis was reported in patients with radiographic axial spondyloarthritis (r-AxSpA). However, a detailed FJ evaluation over the whole spectrum of AxSpA was not performed. We aimed to analyze structural lesions in the FJ of patients with different forms of AxSpA, using computed tomography (CT). METHODS: CT studies of the cervical/thoracic/lumbar spine, or of the chest/abdomen of patients with r-AxSpA or non-radiographic AxSpA (nr-AxSpA) (age ≤ 50 years) were analyzed for the presence of erosions, ankylosis, joint-space narrowing, osteophytes, subchondral sclerosis, subchondral cysts and vacuum phenomenon. Age- and gender-matched subjects without known rheumatic disease who performed spinal CT, formed the control group. Findings were compared between groups, separately for each spinal segment. Further, FJ findings between three subgroups of the axSpA subjects, including r-AxSpA with or without syndesmophytes, and nr-AxSpA, were compared. RESULTS: 959/666 FJs (49/44 patients) were assessed in the AxSpA/control group patients, respectively. The study group consisted of 16 r-AxSpA patients with syndesmophytes and 22 r-AxSpA patients without syndesmophytes, and 11 nr-AxSpA patients. FJ ankylosis was significantly more prevalent in all spinal segments of the r-AxSpA patients with syndesmophytes. Erosions were seen almost exclusively in patients with r-AxSpA. Joint-space narrowing and osteophytes were noted in all segments and all subgroups of AxSpA patients, including those with nrAxSpA. CONCLUSIONS: Disease-specific FJ changes present almost exclusively in patients with r-AxSpA, while degenerative FJ changes are prevalent in all spinal segments and all AxSpA subgroups, suggesting that FJs can be affected early in the disease course.

The association between elevated serum interleukin-22 and the clinical diagnosis of axial spondyloarthritis: A retrospective study.

OBJECTIVE: There is an unmet need for a reliable biomarker for the differentiation of axial spondyloarthritis (AxSpA) from its mimickers. Serum levels of interleukin-22 (IL-22) have previously been found to be significantly elevated in patients with AxSpA compared with healthy individuals or persons with osteoarthritis. METHODS: Consecutive patients with established or suspected AxSpA were enrolled. The clinical data, as well as results of laboratory and imaging studies, were acquired from patients' charts. The final diagnosis of definite or probable SpA, or an alternative diagnosis, was determined, and the serum levels of IL-22 were examined by enzyme-linked immunosorbent immunoassay. RESULTS: Interleukin-22 levels were significantly higher in patients with definite AxSpA (29 patients) compared with patients with alternative diagnoses (14 patients) and healthy volunteers (16 individuals; P < 0.001 for both comparisons). The sensitivity and specificity of the serum IL-22 for the AxSpA diagnosis were 0.68 (95% CI 0.49-0.84) and 0.86 (95% CI 0.68-0.95), respectively, for the cut-off value of 5 pg/mL. In patients with AxSpA, serum IL-22 levels did not correlate with modified Stoke Ankylosing Spondylitis Spinal Score (mSASSS), Bath Ankylosing Spondylitis Disease Activity Index (BASDAI), Ankylosing Spondylitis Disease Activity Score (ASDAS), or serum C-reactive protein. CONCLUSION: Serum IL-22 levels are elevated in patients with the clinical diagnosis of AxSpA and can potentially serve as an independent biomarker for the differentiation of AxSpA from its non-inflammatory mimickers.

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.

External validation and comparison of multiple prognostic scores in allogeneic hematopoietic stem cell transplantation.

Clinical decisions in allogeneic hematopoietic stem cell transplantation (allo-HSCT) are supported by the use of prognostic scores for outcome prediction. Scores vary in their features and in the composition of development cohorts. We sought to externally validate and compare the performance of 8 commonly applied scoring systems on a cohort of allo-HSCT recipients. Among 528 patients studied, acute myeloid leukemia was the leading transplant indication (44%) and 46% of patients had a matched sibling donor. Most models successfully grouped patients into higher and lower risk strata, supporting their use for risk classification. However, discrimination varied (2-year overall survival area under the receiver operating characteristic curve [AUC]: revised Pretransplantation Assessment of Mortality [rPAM], 0.64; PAM, 0.63; revised Disease Risk Index [rDRI], 0.62; Endothelial Activation and Stress Index [EASIx], 0.60; combined European Society for Blood and Marrow Transplantation [EBMT]/Hematopoietic Cell Transplantation-specific Comorbidity Index [HCT-CI], 0.58; EBMT, 0.58; Comorbidity-Age, 0.58; HCT-CI, 0.55); AUC ranges from 0.5 (random) to 1.0 (perfect prediction). rPAM and PAM, which had the greatest predictive capacity across all outcomes, are comprehensive models including patient, disease, and transplantation information. Interestingly, EASIx, a biomarker-driven model, had comparable performance for nonrelapse mortality (NRM; 2-year AUC, 0.65) but no predictive value for relapse (2-year AUC, 0.53). Overall, allo-HSCT prognostic systems may be useful for risk stratification, but individual prediction remains a challenge, as reflected by the scores' limited discriminative capacity.