Comorbidity clusters in patients with rheumatoid arthritis identify a patient phenotype with a favourable prognosis.

OBJECTIVES: We aimed to cluster patients with rheumatoid arthritis (RA) based on comorbidities and then examine the association between these clusters and RA disease activity and mortality. METHODS: In this population-based study, residents of an eight-county region with prevalent RA on 1 January 2015 were identified. Patients were followed for vital status until death, last contact or 31 December 2021. Diagnostic codes for 5 years before the prevalence date were used to define 55 comorbidities. Latent class analysis was used to cluster patients based on comorbidity patterns. Standardised mortality ratios were used to assess mortality. RESULTS: A total of 1643 patients with prevalent RA (72% female; 94% white; median age 64 years, median RA duration 7 years) were studied. Four clusters were identified. Cluster 1 (n=686) included patients with few comorbidities, and cluster 4 (n=134) included older patients with 10 or more comorbidities. Cluster 2 (n=200) included patients with five or more comorbidities and high prevalences of depression and obesity, while cluster 3 (n=623) included the remainder. RA disease activity and survival differed across the clusters, with cluster 1 demonstrating more remission and mortality comparable to the general population. CONCLUSIONS: More than 40% of patients with prevalent RA did not experience worse mortality than their peers without RA. The cluster with the worst prognosis (<10% of patients with prevalent RA) was older, had more comorbidities and had less disease-modifying antirheumatic drug and biological use compared with the other clusters. Comorbidity patterns may hold the key to moving beyond a one-size-fits-all perspective of RA prognosis.

Time Trends in Glucocorticoid Use in Rheumatoid Arthritis During the Biologics Era: 1999-2018.

OBJECTIVES: To examine time trends in glucocorticoid (GC) use among patients diagnosed with rheumatoid arthritis (RA) during the biologic era. METHODS: A population-based inception cohort of RA patients diagnosed during 1999 - 2018 was followed longitudinally through their medical records until death, migration or 12/31/2020. All patients fulfilled 1987 American College of Rheumatology classification criteria for RA. GC start and stop dates were collected along with dosages in prednisone equivalents. The cumulative incidence of GC initiation and discontinuation adjusted for the competing risk of death was estimated. Cox models adjusted for age and sex were used to compare trends between time periods. RESULTS: The study population included 399 patients (71% female) diagnosed in 1999 - 2008 and 430 patients (67% female) diagnosed in 2009 - 2018. GC use was initiated within 6 months of meeting RA criteria in 67% of patients in 1999-2008 and 71% of patients in 2009-2018, corresponding to a 29% increase in hazard for initiation of GC in 2009-2018 (adjusted hazard ratio [HR]: 1.29; 95% confidence interval [CI]: 1.09-1.53). Among GC users, similar rates of GC discontinuation within 6 months after GC initiation were observed in patients with RA incidence in 1999 - 2008 and 2009 - 2018 (39.1% versus 42.9%, respectively), with no significant association in adjusted Cox models (HR: 1.11; 95% CI: 0.93-1.31). CONCLUSION: More patients are initiating GCs early in their disease course now compared to previously. The rates of GC discontinuation were similar, despite the availability of biologics.

Patients with ACPA-positive and ACPA-negative rheumatoid arthritis show different serological autoantibody repertoires and autoantibody associations with disease activity.

Patients with rheumatoid arthritis (RA) can test either positive or negative for circulating anti-citrullinated protein antibodies (ACPA) and are thereby categorized as ACPA-positive (ACPA+) or ACPA-negative (ACPA-), respectively. In this study, we aimed to elucidate a broader range of serological autoantibodies that could further explain immunological differences between patients with ACPA+ RA and ACPA- RA. On serum collected from adult patients with ACPA+ RA (n = 32), ACPA- RA (n = 30), and matched healthy controls (n = 30), we used a highly multiplex autoantibody profiling assay to screen for over 1600 IgG autoantibodies that target full-length, correctly folded, native human proteins. We identified differences in serum autoantibodies between patients with ACPA+ RA and ACPA- RA compared with healthy controls. Specifically, we found 22 and 19 autoantibodies with significantly higher abundances in ACPA+ RA patients and ACPA- RA patients, respectively. Among these two sets of autoantibodies, only one autoantibody (anti-GTF2A2) was common in both comparisons; this provides further evidence of immunological differences between these two RA subgroups despite sharing similar symptoms. On the other hand, we identified 30 and 25 autoantibodies with lower abundances in ACPA+ RA and ACPA- RA, respectively, of which 8 autoantibodies were common in both comparisons; we report for the first time that the depletion of certain autoantibodies may be linked to this autoimmune disease. Functional enrichment analysis of the protein antigens targeted by these autoantibodies showed an over-representation of a range of essential biological processes, including programmed cell death, metabolism, and signal transduction. Lastly, we found that autoantibodies correlate with Clinical Disease Activity Index, but associate differently depending on patients' ACPA status. In all, we present candidate autoantibody biomarker signatures associated with ACPA status and disease activity in RA, providing a promising avenue for patient stratification and diagnostics.

Clinical Outcomes With and Without Plasma Exchange in the Treatment of Rapidly Progressive Interstitial Lung Disease Associated With Idiopathic Inflammatory Myopathy.

BACKGROUND/OBJECTIVE: A subset of patients with idiopathic inflammatory myopathy (IIM) develops highly fatal, rapidly progressive interstitial lung disease (RP-ILD). Treatment strategies consist of glucocorticoid and adjunctive immunosuppressive therapies. Plasma exchange (PE) is an alternative therapy, but its benefit is unclear. In this study, we aimed to determine whether PE benefited outcomes for patients with RP-ILD. METHODS: In this medical records review study, we compared baseline characteristics and clinical outcomes for 2 groups of patients with IIM-related RP-ILD: those who received and did not receive PE. RESULTS: Our cohort consisted of 15 patients, 9 of whom received PE. Baseline demographic characteristics and severity of lung, skin, and musculoskeletal disease between the 2 groups of patients were not significantly different. Five patients required mechanical ventilation (2, PE; 3, no PE). Plasma exchange was generally a third-line adjunctive treatment option. The PE group had a longer median (interquartile range) hospitalization (27.0 [23.0-36.0] days) than the non-PE group (12.0 [8.0-14.0] days) ( p = 0.02). There was a potential benefit in 30-day mortality improvement in those receiving PE (0% vs 33%, p = 0.14), with a statistically significant improvement in 2 important composite end points including 30-day mortality or need for lung transplant (0% vs 50%, p = 0.04) and 1-year mortality or need for lung transplant or hospital readmission for RP-ILD in those receiving PE (22% vs 83%, p = 0.04). CONCLUSIONS: Plasma exchange may be an underutilized, safe salvage therapy for patients with IIM-related RP-ILD when other immunosuppressive therapies fail.

Evolving Role of Dual-Energy CT in the Clinical Workup of Gout: A Retrospective Study.

BACKGROUND. Dual-energy CT (DECT) allows noninvasive detection of monosodium urate (MSU) crystal deposits and has become incorporated into the routine clinical evaluation for gout at many institutions over the past decade. OBJECTIVE. The purpose of this study was to compare two time periods over the past decade in terms of radiologists' interpretations of DECT examinations performed for the evaluation of gout and subsequent clinical actions. METHODS. This retrospective study included 100 consecutive adult patients who underwent DECT to evaluate for gout in each of two periods (one beginning in March 2013 and one beginning in September 2019). Examinations performed in 2013 were conducted using a second-generation DECT scanner (80 kV [tube A] and 140 kV [tube B] with a 0.4-mm tin filter), and those performed in 2019 were conducted using a third-generation DECT scanner (80 kV [tube A] and 150 kV [tube B] with a 0.6-mm tin filter) that provides improved spectral separation. Original DECT reports were classified as positive, negative, or equivocal for MSU crystals indicative of gout. Joint aspirations occurring after the DECT examinations were recorded on the basis of findings from medical record review. A single radiologist performed a post hoc retrospective blinded image review, classifying examinations as positive, negative, or equivocal. RESULTS. In 2013, 44.0% of DECT examinations were interpreted as positive, 23.0% as negative, and 33.0% as equivocal; in 2019, 37.0% were interpreted as positive, 47.0% as negative, and 16.0% as equivocal (p < .001). The frequency of joint aspiration after DECT was 14.0% in 2013 versus 2.0% in 2019 (p = .002), and that after DECT examinations with negative interpretations was 17.4% in 2013 versus 2.1% in 2019 (p = .02). In post hoc assessment by a single radiologist, the distribution of interpretations in 2013 was positive in 49.0%, negative in 22.0%, and equivocal in 29.0%, and in 2019 it was positive in 39.0%, negative in 50.0%, and equivocal in 11.0% (p < .001). CONCLUSION. When DECT examinations performed for gout in 2013 and 2019 were compared, the frequency of equivocal interpretations was significantly lower in 2019, possibly in relation to interval technologic improvements. Negative examinations were less frequently followed by joint aspirations in 2019, possibly reflecting increasing clinical acceptance of the DECT results. CLINICAL IMPACT. The findings indicate an evolving role for DECT in the evaluation of gout after an institution's routine adoption of the technology for this purpose.

Tumor necrosis factor inhibitor (TNFi) persistence and reasons for discontinuation in a predominantly male cohort with axial spondyloarthritis.

Although tumor necrosis factor inhibitors (TNFi) have favorably altered the treatment landscape for patients with axial spondyloarthritis (axSpA), there is limited data regarding TNFi persistence and reasons for discontinuation. This is an observational time-to-event study utilizing data collected for a prospective multiple-disease registry of US Veterans with axSpA treated with TNFi therapies and recruited over a 10 year period. Clinical, serological, and comorbid parameters were collected. Corporate Data Warehouse Pharmacy files provided courses of the 5 TNFi agents, and response to treatment was documented. Individual TNFi persistence was established utilizing univariate and multivariate Cox proportional models, and reasons for discontinuation were obtained by physician chart review. Two-hundred and fifty-five axSpA patients received 731 TNFi courses. A majority of patients (84.3%) had TNFi persistence at 12 months; 63.5% and 47.1% at 24 and 36 months, respectively. Compared to adalimumab, infliximab demonstrated greater persistence, certolizumab the least. Age, smoking status, BMI, comorbidity burden, inflammatory markers and HLA-B27 did not predict TNFi persistence or discontinuation. Stroke and peripheral arterial disease increased the probability of TNFi discontinuation. Secondary non-response (SNR) was the most common reason for discontinuation (46% of all courses); non-adherence (6%) and clinical remission (2%) were uncommon. Pain score at enrollment, myocardial infarction, African American race and inflammatory bowel disease (IBD) predicted TNFi response. While initial persistence of TNFi treatment was high, a large proportion of the patients discontinued initial TNFi therapy by 3 years, primarily due to loss of efficacy. While further research identifying potential predictors of TNFi discontinuation in axSpA is warranted, access to alternate disease-modifying therapies is needed.

Differential Diagnosis and Workup of Monocytosis: A Systematic Approach to a Common Hematologic Finding.

PURPOSE OF REVIEW: Monocytosis is a frequently encountered clinical condition that needs appropriate investigation due to a broad range of differential diagnoses. This review is meant to summarize the latest literature in the diagnostic testing and interpretation and offer a stepwise diagnostic approach for a patient presenting with monocytosis. RECENT FINDINGS: Basic studies have highlighted the phenotypic and functional heterogeneity in the monocyte compartment. Studies, both translational and clinical, have provided insights into why monocytosis occurs and how to distinguish the different etiologies. Flow cytometry studies have illustrated that monocyte repartitioning can distinguish chronic myelomonocytic leukemia, a prototypical neoplasm with monocytosis from other reactive or neoplastic causes. In summary, we provide an algorithmic approach to the diagnosis of a patient presenting with monocytosis and expect this document to serve as a reference guide for clinicians.

Giant cell arteritis associated with inflammatory bowel disease: a case-series and review of the literature.

To describe the clinical characteristics, management, and outcome of a series of patients with giant cell arteritis (GCA) and inflammatory bowel disease (IBD). Patients with both GCA and IBD evaluated between 1/1/1996 and 12/30/2018 were retrospectively identified. Clinical characteristics, laboratory parameters, radiologic features, histopathology, management and outcomes were abstracted. A systematic literature review identifying patients with IBD and GCA was performed via a Medline and EMBASE search from inception through December 31 2019. Six patients were identified with GCA and IBD (66% male). Five (83%) had ulcerative colitis (UC) and one had Crohn's disease (CD). Diagnosis of IBD preceded GCA in four patients with an average interval of 30 years (range 14-42). Average time to IBD diagnosis in those with prior GCA diagnosis was 1.5 years. During mean follow-up of 4.3 years, GCA relapse was infrequent with only one patient with relapse observed. Systematic literature review identified six additional patients with confirmed coexistence of GCA and IBD. Similar to the current series, male sex was more common and ulcerative colitis was the predominant IBD phenotype. The current study reports findings from the largest single-institution case-series of co-existent GCA and IBD. In contrast to Takayasu arteritis with co-existent IBD, which displays a predilection for female sex and Crohn's disease phenotype, both the current study and review of literature demonstrate a stronger association of GCA with male sex and ulcerative colitis. Further studies addressing a potential pathophysiologic connection between GCA and IBD are suggested.

Autoimmunity, Clonal Hematopoiesis, and Myeloid Neoplasms.

Clonal hematopoiesis has been linked with the development of hematologic malignancy and atherosclerotic cardiovascular disease; however, the association with autoimmune diseases remains to be defined. The link between autoimmune diseases and myeloid neoplasms (MNs) is complex, often multifactorial, and seems bidirectional. The limited data suggest an increased risk of MNs in rheumatoid arthritis and systemic lupus erythematosus. Paraneoplastic manifestations of MN include arthritis, vasculitis, and connective tissue disease. Treatment options for autoimmune disease such as cyclophosphamide and azathioprine have been associated with MNs, whereas the data for methotrexate and tumor necrosis factor inhibitors are equivocal.

Sonography of active rheumatoid arthritis during pregnancy: a case report and literature review.

Disease activity in rheumatoid arthritis usually subsides in pregnancy, however a subset of patients have worsened symptoms with joint pain and swelling. Monitoring and mitigating disease activity in pregnancy is important for preventing deforming structural changes which can affect the ability of the patient to care for themselves and the newborn. Ultrasound is a safe and low-cost imaging modality for detecting active changes from an inflammatory arthritis, which can help guide management. We describe a case of an acute disease flare during pregnancy, readily detected with ultrasound, and present a review of sonographic evaluation of rheumatoid arthritis in pregnancy.

The Evaluation of Syncope in a Predominantly Black Population: Focus on Neuroimaging.

BACKGROUND: Current guidelines do not support the routine use of computed tomography (CT) scan of the head in the diagnostic workup of syncope. There is a lack of research to support whether these guidelines apply to the Black population. AIMS: This study aims to evaluate the yield of neuroimaging in the evaluation of Syncope in a predominantly Black patient population and to test whether current guidelines based on studies conducted in other populations hold true in this group. MATERIAL AND METHODS: A retrospective review of records of 151 patients admitted to a University Hospital with Syncope from 2011 to 2014 was performed. Data collected include CT head, magnetic resonance imaging of the brain, magnetic resonance angiogram, electroencephalogram, and orthostatic vital signs. Demographic data, admitting service, and comorbid conditions were identified. Syncope was classified as cardiogenic, orthostatic, vasovagal, situational, or undetermined. Statistical analysis was performed to determine which diagnostic tools were useful in identifying the potential causes of syncope. Data analysis was conducted using the Statistical Analysis System software 9.3 (SAS Institute, Cary, NC) and Statistical Analysis and Graphics (NCSS 9.0.7, Kaysville, UT). RESULTS: One hundred and twenty eight (84.8%) of the patients were Black. The average age was 56.62 ± 18.78 standard deviation and 68.2% (103) were female. One hundred and fourteen patients (75.5%) had a CT brain. Five out of 114 patients had an acute abnormality on CT (4.4%). Only 1 of these 5 patients had an abnormality that was related to syncope. CT brain (P = 0.978) was not found to be predictive of underlying etiology of syncope despite high frequency of use. CONCLUSIONS: CT head was not useful in determining the etiology of syncope in a predominantly Black population. Current guidelines and studies conducted in other populations have detected similar findings.