The latest medical research on Rheumatology

The research magnet gathers the latest research from around the web, based on your specialty area. Below you will find a sample of some of the most recent articles from reputable medical journals about rheumatology gathered by our medical AI research bot.

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Four Cases of Lupus Associated Psychosis.

Arthritis Rheumatol

We read with great interest the paper by Hanly et al (1) discussing lupus-associated psychosis. The authors present data from the largest prospecti...

Facial papular lesions in a woman with granulomatosis with polyangiitis.

Arthritis Rheumatol

A 39-years-old woman, was diagnosed with limited pulmonary granulomatosis with polyangiitis (GPA) five years ago. She was treated with methotrexate...

The Effect of Therapy on Radiographic Progression in Axial Spondyloarthritis: A Systematic Review and Meta-Analysis.

Arthritis Rheumatol

To investigate effect of therapies on radiographic progression in axial spondyloarthritis (axSpA).

Comprehensive database search for studies assessing radiographic progression in axSpA (particular treatment vs. no treatment of interest) was performed. Study-specific standardized mean differences were estimated and combined using random-effects model.

Twenty four studies were included; 18 with tumor necrosis factor inhibitors (TNFi), 8 with non-steroidal anti-inflammatory drugs (NSAIDs), and 1 with secukinumab. Spinal radiographic progression was not significantly different among TNFi-treated vs. biologic naïve populations at 2 years (mSASSS difference= -0.73, 95% CI -1.52 to 0.12, I2 =28%) and at ≥4 years (mSASSS difference= -2.03, 95% CI -4.63 to 0.72, I2 =63%). Sensitivity analysis restricted to studies with low risk of bias showed a significant difference at ≥4 years (mSASSS difference= -2.17, 95% CI -4.19 to -0.15). No significant difference was observed between NSAIDs vs. control (mSASSS difference= -0.30, 95% CI =-2.62 to 1.31, I2 =71%), or secukinumab vs. biologic naïve (mSASSS difference= -0.34, 95% CI -0.85 to 0.17). There were not enough studies on nr-axSpA or SIJ progression for analysis.

Although no significant protective effect of TNFi treatment on spinal radiographic progression of AS at 2 and ≥4 years was seen, analysis restricted to studies with low risk of bias showed a protective effect at ≥4 years. Therefore, long-term TNFi exposure might have radiographic progression benefit. No difference was seen with NSAIDs or secukinumab at 2 years. Future studies should explore effect of biologics on radiographic progression in early axSpA and nr-axSpA, and with long-term exposure.

Reply.

Arthritis Rheumatol

We would like to thank Dr. Park and colleagues for their interest in our manuscript on lupus psychosis and for their description of Four Cases of L...

Methionine commits cells to differentiate into plasmablasts through epigenetic regulation of BTB and CNC homolog 2 by the methyltransferase enhancer of zeste homolog 2.

Arthritis Rheumatol

Plasmablasts play important roles in autoimmune diseases, including systemic lupus erythematosus (SLE). Activation of mechanistic target of rapamycin complex 1 (mTORC1) is regulated by amino acid levels. In patients with SLE, mTORC1 is activated in B cells and modulates plasmablast differentiation. However, the detailed mechanisms of amino acid metabolism in plasmablast differentiation remain elusive. Here, we evaluated the effects of methionine in human B cells.

Purified CD19+ cells from healthy donors (n=21) or patients with SLE (n=35) were cultured with Toll-like receptor 7/9 ligand, IFN-α, and B cell receptor crosslinking, and we determined the types of amino acids that were important for plasmablast differentiation and amino acid metabolism. We also identified the transcriptional regulatory mechanisms induced by amino acid metabolism and assessed B cell metabolism and its relevance to SLE.

The essential amino acid methionine strongly committed cells to plasmablast differentiation. In the presence of methionine, Syk and mTORC1 activation synergistically induced methyltransferase enhancer of zeste homolog 2 (EZH2) expression. EZH2 induced H3K27me3 at BTB and CNC homolog 2 (BACH2) loci and suppressed BACH2 expression, leading to induction of B lymphocyte-induced maturation protein-1 and X-box binding protein 1 expression and plasmablast differentiation. CD19+ cells from patients with SLE overexpressed EZH2, which was correlated with disease activity and autoantibody production.

Our results showed that methionine activated signaling by controlling immunological metabolism in B cells and played an important role in the differentiation of B cells into plasmablasts through epigenome modification of BACH2 by the methyltransferase EZH2.

Identification of cartilage microbial DNA signatures and associations with knee and hip osteoarthritis.

Arthritis Rheumatol

Alterations of the gut microbiota have been implicated in many forms of arthritis, but an examination of cartilage microbial patterns have not been performed. The objective of this study was to characterize the microbial DNA profile of articular cartilage and determine changes associated with osteoarthritis (OA).

16s rRNA gene deep sequencing was performed on eroded and intact cartilage samples from knee and hip OA patients and cadaveric controls. Microbial DNA diversity was assessed, groups compared, and metagenomic profiles reconstructed. Confirmation was performed in an independent cohort by clade-specific qPCR. Human results were compared to cartilage from OA-susceptible C57BL6 and OA-resistant MRL/MpJ mice. Germ-free C57BL6 mouse cartilage was analyzed as a methodological control.

Alpha diversity was reduced in human OA vs. control (p<0.0001), and in hip samples vs. knees (p<0.0001). Numerous clades were different in human OA vs. controls, similar findings were noted in murine B6 vs. MRL comparisons. Hip samples were microbiologically distinct from knee samples. OA microbial DNA demonstrated increased Gram-negative constituents (p=0.02). Functional analysis demonstrated increases in lipopolysaccharide production (p=9.9E-3), phosphatidylinositol signaling (p=4.2E-4), and nitrogen metabolism (p=8E-3) and decreases in sphingolipid metabolism (p=7.7E-4) associated with OA.

Our study reveals a microbial DNA signature in human and mouse cartilage. We find alterations in this signature, including increases in Gram-negative constituents, during the development and progression of human OA. Furthermore, we identified strain-specific signatures within mouse cartilage that mirror human patterns. The establishment and potential pathogenic role of these DNA signatures deserve further study.

A 21-Year-Old Woman with Joint Pain and Skin Ulceration.

Arthritis Care Res

The illness started with pain and stiffness in her bilateral hands and wrists four months prior, with progression to bilateral elbows, knees, and a...

Elevated anti-citrullinated protein antibodies prior to rheumatoid arthritis diagnosis and risks for chronic obstructive pulmonary disease or asthma.

Arthritis Care Res

To investigate elevation of anti-citrullinated protein antibodies (ACPA) before RA diagnosis and risks for chronic obstructive pulmonary disease (COPD) or asthma.

We performed a matched cohort study nested within the Nurses' Health Studies among women who donated blood. Women with incident RA after blood draw (self-reported then confirmed by medical records) were each matched to three controls by age, cohort, year, and menopausal factors. Pre-RA ACPA+ was defined as >99th percentile of control distribution by a research assay or by CCP2 in a subset. Incident COPD and asthma after index date (date of blood draw) were identified by questionnaires. Cox regression estimated HRs for incident COPD or asthma (in separate analyses) associated with pre-RA, pre-RA ACPA+, or pre-RA ACPA- phenotypes each compared to their matched non-RA controls.

We analyzed 283 pre-RA women and 842 controls; blood was donated mean of 9.7 years (SD 5.8) before RA diagnosis. Fifty-nine women (20.8%) were pre-RA ACPA+. There were 107 cases of incident COPD and 105 incident asthma cases during 21,489 person-years of follow-up. Pre-RA ACPA+ was associated with increased COPD risk (HR 3.04, 95%CI 1.33,7.00) after adjusting for covariates including smoking pack-years. Pre-RA ACPA+ had a HR for asthma of 1.74 (multivariable 95%CI 0.72,4.24), similar to the risk of asthma for pre-RA ACPA- (HR 1.65, 95%CI 1.11,2.46).

Women with elevated ACPA before RA diagnosis had increased risk for developing COPD compared to controls. Women who later developed RA were more likely to develop asthma, regardless of pre-RA ACPA status.

Community Deprivation Index and Discharge Destination after Elective Hip Replacement.

Arthritis Care Res

To examine how the deprivation level of the community in which one lives influences discharge disposition and the odds of 90-day readmission after elective THA.

We performed a retrospective cohort study on 84,931 patients who underwent elective THA in the Pennsylvania Health Care Cost Containment Council database from 2012 to 2016. We used adjusted binary logistic regression models to test the association between community ADI and patient discharge destination as well as 90-day readmission. We included an interaction term for community ADI and patient race in our models to assess the simultaneous effect of both on the outcomes.

After adjusting for patient and facility level characteristics, patients from high ADI (most disadvantaged) communities, compared to patients from low ADI (least disadvantaged) communities, were more likely to be discharged to an institution as opposed to home for post-op care and rehab (age <65: aOR = 1.47; age ≥65; aOR = 1.31; both p<0.001). The interaction effect of patient race and ADI on discharge destination was statistically significant in those ≥ 65 years of age, but not in patients < 65 years. The association of ADI on 90-day readmission was not statistically significant.

In this statewide sample of patients who underwent elective THA, the level of deprivation of the community in which patients reside influences their discharge disposition, but not their odds of 90-day readmission to an acute care facility.

Is a stepped-care intervention effective in overweight and obese people with medial tibiofemoral osteoarthritis? The STrEAMline study: A randomised controlled trial.

Arthritis Care Res

To test the effectiveness of a 32-week stepped-care intervention on disease remission rates in overweight and obese people with medial tibiofemoral osteoarthritis (OA) compared to control.

In this randomised controlled trial, eligible participants were ≥50 years-old with a body mass index ≥28 kg/m2 and radiographic evidence of medial tibiofemoral OA. Participants were randomised to stepped-care (n=87) or control group (n=84). The stepped-care group received a two-step intervention. The first step consisted of an 18-week diet and exercise program. The second step consisted of four treatment subgroups: (1) diet and exercise maintenance; (2) cognitive behavioural therapy (CBT); (3) unloader knee brace and; (4) muscle strengthening exercises. Allocation into subgroups was based on disease remission state and clinical characteristics. The primary endpoint was disease remission rate (yes/no) at 32-weeks, which was reached when participants presented patient acceptable symptom state (PASS) for pain plus the patient global assessment of disease activity and/or functional impairment.

Disease remission at 32-weeks was achieved by 18 out of 68 (26%) in the control group and 32 out of 82 (39%) in the stepped-care group (difference 12.6%, 95% CI: -2.3 to 27.4, p=0.10). The stepped-care group showed an improvement in pain and function between baseline and 20-weeks. While functional improvement was maintained at 32-weeks, pain levels tended to get worse between weeks 20 and 32.

The proposed intervention did not promote a significant difference in the rate of disease remission in comparison to control group for overweight or obese people with medial tibiofemoral OA.

Health Care Utilization for Musculoskeletal Issues During the Pre-diagnosis Period in Psoriatic Arthritis - A Population-Based Study.

Arthritis Care Res

Information about the pre-diagnosis period in psoriatic arthritis (PsA) is limited. We compared health care utilization related to musculoskeletal issues during a 5-year period prior to the diagnosis of PsA versus subjects with no prior inflammatory arthritis within a primary care setting.

We conducted a population-based, matched cohort study using electronic medical records and administrative data in Ontario, Canada. Age- and sex-matched cohorts of PsA patients and comparators from the same family physicians were assembled. Comparators were not allowed to have prior spondyloarthritis, ankylosing spondylitis, or rheumatoid arthritis billing code diagnoses. The study outcomes included health care utilization and costs related to non-specific musculoskeletal issues during a 5-year period prior to the index date.

We studied 462 PsA patients and 2310 matched comparators. The odds ratio (OR) related to visiting a primary care physician for nonspecific musculoskeletal issues in patients with PsA was 2.14 (95% CI 1.73, 2.64) in the year immediately preceding the index date and was similarly elevated up to 5 years prior. The OR related to using other musculoskeletal-related health care services, including musculoskeletal specialists visits, joint injections, joint imaging, and emergency department visits, were higher in PsA as early as 5 years preceding the index date. Total and musculoskeletal-related healthcare costs prior to the index date were higher in patients with PsA versus comparators.

A prodromal PsA phase, characterized by non-specific musculoskeletal symptoms may exist. Further study is needed to determine if this represents a window for earlier diagnosis of PsA.

Comparing the patient reported physical function outcome measures in a real-life international cohort of patients with psoriatic arthritis.

Arthritis Care Res

We evaluated the psychometric properties of three patient-reported outcomes (PROMs) to assess the physical function in psoriatic arthritis (PsA).

Data available for Health Assessment Questionnaire-disability index (HAQ-DI), Physical component summary score of SF-12 (PCS12) and functional capacity of Psoriatic Arthritic Impact of Disease Instrument (PsAID-FC) from a longitudinal study in 14 countries of consecutive adults with definite PsA with ≥ 2 years of duration. The score distribution, construct validity, responsiveness and thresholds of meaning of the PROMs were evaluated.

At baseline, 414 subjects (52% male) were analysed. The mean (SD) age and duration of illness were 52.4 (12.5) and 10.9 (8.1) years. Ceiling effects were noted in 31% and 21% of patients for HAQ-DI and PsAID-FC; floor effects were minimal. All three PROMs met a priori hypotheses for construct validity. After a median (IQR) follow-up of 4.1 (2.7) months in 350 patients, 27%, 54% and 18% of patients reported themselves improved, not changed and worse, respectively. Change scores were statistically different for groups for worsening versus no-change for all PROMs. PsAID-FC was more sensitive to change than the other two PROMs. Comparing groups with worsening condition to no-change, the standardized response mean square ratios (SRM2 ) were for HAQ-DI: 29.9, PCS12: 16.7 and PsAID-FC: 40.1, respectively.

HAQ-DI, PCS12 and PsAID-FC are valid measures of function for PsA. PsAID-FC, a single question, performed similarly to the other PROMs and may be an additional option to measure PsA-specific physical function.