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Preview: Rheumatology - current issue

Rheumatology Current Issue





Published: Mon, 18 Sep 2017 00:00:00 GMT

Last Build Date: Sat, 23 Sep 2017 02:50:27 GMT

 









Sarcopenic obesity is more prevalent in osteoarthritis than rheumatoid arthritis: are different processes involved?

2017-08-11

Rheumatology key message
  • Sarcopenia is highly prevalent in osteoarthritis and rheumatoid arthritis.






Presentations and outcomes of juvenile dermatomyositis patients admitted to intensive care units

2017-08-02

Rheumatology key message
  • JDM exacerbations, especially vasculopathy-related complications, were the main cause of admission to the intensive care unit.



Infrapatellar fat pad features in osteoarthritis: a histopathological and molecular study

2017-07-31

Abstract
Objective
The infrapatellar fat pad (IFP) is considered a local producer of adipocytokines, suggesting a potential role in OA. The objective of this study was to evaluate the histopathological and molecular characteristics of OA IFPs compared with controls.
Methods
The histopathological characteristics of IFPs were evaluated in patients undergoing total knee replacements and in control patients (without OA), considering the following parameters: presence of inflammatory cells, vascularization, adipose lobules dimension and thickness of the interlobular septa. Immunohistochemistry was performed to evaluate VEGF, monocyte chemotactic protein 1 (MCP-1) and IL-6 proteins. Quantitative real time PCR was performed to evaluate the expression levels of adipocytokines in the OA IFPs.
Results
OA IFPs showed an increase in inflammatory infiltration, vascularization and thickness of the interlobular septa compared with controls. VEGF, MCP-1 and IL-6 proteins were higher in OA IFPs compared with in controls. Inflammatory infiltration, hyperplasia, vascularization and fibrosis were increased in OA IFP synovial membranes compared with in those of controls. VEGF protein levels were associated with an increased number of vessels in the OA IFPs, while MCP-1 and IL-6 protein levels were associated with higher grades of inflammatory infiltration. Leptin levels were positively correlated with adiponectin and MCP-1expression, while adiponectin positively correlated with peroxisome proliferative activated receptor gamma, MCP-1 and IFP vascularity. MCP-1 showed a positive correlation with peroxisome proliferative activated receptor gamma. IFP lobules dimensions were positively correlated with IL-6 expression and negatively with thickness of interlobular septa. VEGF mRNA levels were positively correlated with increased synovial vascularity.
Conclusions
OA IFPs and synovial membranes are more inflamed, vascularized and fibrous compared with those of control patients (without OA).



Comment on: Patterns of interstitial lung disease and mortality in rheumatoid arthritis

2017-07-27

Sir, We are writing with reference to the excellent recent paper by Zamora-Legoff et al. from the Mayo Clinic on ‘Patterns of interstitial lung disease and mortality in rheumatoid arthritis’ [1]. The overall 5-year survival of 181 patients was 59.7% and they identified age, disease duration and baseline gas transfer as important predictors of premature mortality, although a number of other factors including the pattern of lung disease did not significantly affect outcome in their study. The population demographics are very similar to those in a UK-based BRILL cohort of 290 patients [2] but the survival figures are quite different. One reason for this may be the variation in therapeutic exposure between the two patient groups. The Mayo group reported biologic usage among most of their patients, with 47% receiving anti-TNF therapy, 18% rituximab and 7% abatacept. There were also high rates of reported usage of oral steroids (51%) and azathioprine (43%) that may have impacted on outcome.



Comment on: Patterns of interstitial lung disease and mortality in rheumatoid arthritis: reply

2017-07-27

Sir, We appreciate the observations and contribution of Kelly and Iqbal [1] regarding the possible effects of rituximab and other biologics on the development and progression of lung disease in patients with new onset RA.



Reproducibility of the scleroderma pattern assessed by wide-field capillaroscopy in subjects suffering from Raynaud’s phenomenon

2017-07-27

Abstract
Objectives
The aim of this work was to study inter- and intra-observer agreement for the diagnosis of scleroderma pattern by wide-field capillaroscopy.
Methods
Images were taken from 50 patients known to have SSc and 50 controls consulting for RP who did not have SSc. These images were rated simultaneously by 11 experienced vascular medicine physicians as scleroderma pattern or not. Two weeks later, 7 of the 11 observers again rated the same images.
Results
Inter-observer agreement was almost perfect between the 11 observers (κ 0.86 ± 0.01), and the proportion of concordant observations was 79% (70–87). When each observer was compared with the reference, agreement was also almost perfect: κ coefficient 0.92 ± 0.03 and proportion of concordant observations 79% (70–87). Intra-observer agreement was also almost perfect: median κ coefficient 0.94 (0.78–0.96) and median proportion of concordant observations 97% (89–98).
Conclusion
Excellent inter- and intra-observer agreement was obtained in experienced vascular physicians for the diagnosis of capillaroscopic landscape by wide-field nailfold capillary microscopy.



Comparing biosimilar SB2 with reference infliximab after 54 weeks of a double-blind trial: clinical, structural and safety results

2017-07-25

Abstract
Objectives
SB2 is a biosimilar to the reference infliximab (INF). Similar efficacy, safety and immunogenicity between SB2 and INF up to 30 weeks were previously reported. This report investigates such clinical similarity up to 54 weeks, including structural joint damage.
Methods
In this phase III, double-blind, parallel-group, multicentre study, patients with moderate to severe RA despite MTX were randomized (1:1) to receive 3 mg/kg of either SB2 or INF at 0, 2, 6 and every 8 weeks thereafter. Dose escalation by 1.5 mg/kg up to a maximum dose of 7.5 mg/kg was allowed after week 30. Efficacy, safety and immunogenicity were measured at each visit up to week 54. Radiographic damage evaluated by modified total Sharp score was measured at baseline and week 54.
Results
A total of 584 patients were randomized to receive SB2 (n = 291) or INF (n = 293). The rate of radiographic progression was comparable between SB2 and INF (mean modified total Sharp score difference: SB2, 0.38; INF, 0.37) at 1 year. ACR responses, 28-joint DAS, Clinical Disease Activity Index and Simplified Disease Activity Index were comparable between SB2 and INF up to week 54. The incidence of treatment-emergent adverse events and anti-drug antibodies were comparable between treatment groups. Such comparable trends of efficacy, safety and immunogenicity were consistent from baseline up to 54 weeks. The pattern of dose increment was also comparable between SB2 and INF.
Conclusion
SB2 maintained similar efficacy, safety and immunogenicity with INF up to 54 weeks in patients with moderate to severe RA. Radiographic progression was comparable at 1 year.
Trial registration
ClinicalTrials.gov (http://clinicaltrials.gov; NCT01936181) and EudraCT (https://www.clinicaltrialsregister.eu; 2012-005733-37)



Comment on: Cumulative immunosuppressant exposure is associated with diversified cancer risk among 14 832 patients with systemic lupus erythematosus

2017-07-24

Sir, We read with interest the study by Hsu et al. [1]. The authors’ use of catastrophic illness certificates is an admirable way of improving SLE identification within administrative data, although it is noteworthy that almost half of the subjects had an overlap with another rheumatic disease.



Factors influencing fetal cardiac conduction in anti-Ro/SSA-positive pregnancies

2017-07-24

Abstract
Objectives
Congenital heart block (CHB) develops in 1–2% of anti-Ro/SSA-positive pregnancies and has a recurrence rate of 12–20%, which indicates that factors other than maternal autoantibodies are crucial for CHB to occur. Here, we aimed to evaluate the influence of factors previously associated with CHB on the occurrence of milder forms of fetal cardiac conduction disturbances, shown to occur in up to 30% of anti-Ro/SSA-positive pregnancies, and on neonatal outcome in a large cohort of prospectively followed pregnancies.
Methods
The association of maternal age, season of the year and history of atrioventricular block (AVB) with the development of fetal Doppler and neonatal ECG conduction disturbances was evaluated in 212 anti-Ro52/SSA-positive singleton pregnancies.
Results
Maternal age was significantly higher in AVB II–III pregnancies but was not correlated with fetal AV time intervals in fetuses without signs of AVB II–III. AV time intervals of fetuses surveilled during the winter were significantly longer than those of fetuses surveilled during the summer. Fetal AV time intervals in consecutive pregnancies from the same women were significantly correlated. A history of AVB II–III was associated with significantly longer AV time intervals, and AVB I–III was observed at birth in 38% of babies born after a sibling with abnormal fetal AV conduction.
Conclusion
Our study shows that AV time intervals in anti-Ro/SSA antibody-exposed fetuses during the CHB risk period are influenced by the season of the year, and reveals that the recurrence of conduction disturbances in antibody-exposed fetuses is higher than previously reported when milder forms are taken into account.



Clinical characteristics of inflammatory ocular disease in anti-neutrophil cytoplasmic antibody associated vasculitis: a retrospective cohort study

2017-07-24

Abstract
Objective
To characterize the clinical correlates and outcome of inflammatory ocular disease (IOD) among patients with ANCA-associated vasculitides (AAV).
Methods
Medical records of potential cases of AAV seen at Mayo Clinic from 2003 to 2013, inclusive, were reviewed to identify confirmed cases meeting the diagnosis of AAV using the Chapel Hill Consensus Conference 2012 descriptors. Records of confirmed cases of AAV were then further reviewed for IOD, and clinical characteristics, treatment and outcomes abstracted.
Results
A total of 1171 confirmed cases of AAV were identified of which 183 patients (mean age 49.0 years; 51% female; 95% Caucasian) had IOD. The most common manifestation of IOD was injection of the eye (57%) followed by eye pain (46%) and visual acuity loss (18%). Scleritis was the most common type of IOD (22%) followed by episcleritis (21%), orbital inflammation (18%), lacrimal duct stenosis (10%) and uveitis (9%). Oral glucocorticoids were used to treat IOD in the majority of patients (96%). CYC and rituximab were the most frequently used immunosuppressive agents (54 and 36%, respectively). Of those with orbital inflammation, 52% underwent therapeutic surgical intervention. Clinical remission of IOD was achieved in 91% of patients but relapses were seen in 23%. Significant visual acuity loss was observed in only six patients.
Conclusion
IOD is a common manifestation of AAV and seen in about 16% of patients with AAV. Scleritis, episcleritis and orbital inflammation are the most common subtypes. Most patients respond well to glucocorticoids and immunosuppression, but relapse of IOD is common.



Cost effectiveness analysis of HLA-B*58:01 genotyping prior to initiation of allopurinol for gout

2017-07-14

Abstract
Objective
To determine whether prospective testing for HLA-B*58:01, as a strategy to prevent serious adverse reactions to allopurinol in patients with gout, is cost-effective from the perspective of the National Health Service in the UK.
Methods
A systematic review and meta-analysis for the association of HLA-B*58:01 with cutaneous and hypersensitivity adverse drug reactions informed a decision analytic and Markov model to estimate lifetime costs and outcomes associated with testing vs standard care (with febuxostat prescribed for patients who test positive). Scenario analyses assessed alternative treatment assumptions and patient populations.
Results
The number of patients needed to test to prevent one case of adverse drug reaction was 11 286 (95% central range (CR): 2573, 53 594). Cost and quality-adjusted life-year (QALY) gains were small, £103 (95% CR: £98, £106) and 0.0023 (95% CR: −0.0006, 0.0055), respectively, resulting in an incremental cost-effectiveness ratio (ICER) of £44 954 per QALY gained. The probability of testing being cost-effective at a threshold of £30 000 per QALY was 0.25. Reduced costs of testing or febuxostat resulted in an ICER below £30 000 per QALY gained. The ICER for patients with chronic renal insufficiency was £38 478 per QALY gained.
Conclusion
Routine testing for HLA-B*58:01 in order to reduce the incidence of adverse drug reactions in patients being prescribed allopurinol for gout is unlikely to be cost-effective in the UK; however testing is expected to become cost-effective with reductions in the cost of genotyping, and with the future availability of cheaper, generic febuxostat.



Analysis of dedicated sacroiliac views to improve reliability of conventional pelvic radiographs

2017-07-14

Abstract
Objective
To compare the antero-posterior (AP) pelvis view with the Ferguson view of the SI joint in order to resolve whether one modality has a clear advantage for grading of sacroiliitis.
Methods
One hundred and nine patients fulfilling Assessment of SpondyloArthritis international Society (ASAS) criteria for axial spondyloarthritis who had AP pelvis and Ferguson views on the same day were identified from an axial spondyloarthritis clinic registry. Two rheumatologists independently scored the AP pelvis and Ferguson views according to modified New York (NY) criteria. Intra- and inter-reader agreements were obtained for both evaluations by using the kappa statistic and intraclass correlation coefficient (ICC). Any change in diagnostic category dictated by the Ferguson vs the AP pelvis views was also evaluated.
Results
A total of 266 radiographs were read from 109 patients. Intra-observer reliability of the observers showed similar ICC scores; this was also reflected in the kappa for diagnosis of AS fulfilling modified NY criteria between the observers. The inter-rater agreement showed similar kappa values between the two modalities. When separately evaluating SI joints with score grading of 0–2, grade 2 showed the lowest kappa, reaching a low of 0.1 and 0.19 for the right SI joint for Ferguson and AP pelvis views, respectively. Both modalities were concordant diagnostically; reclassification from AS to non-AS and vice versa was in the range 5–11%.
Conclusion
There was general agreement between the Ferguson and AP pelvis X-ray ICC and kappa scores. Either modality can be employed to evaluate the SI joint for sacroiliitis with the Ferguson view showing no clear superiority over the standard AP pelvis view.



Risk factors of serious infections in patients with rheumatoid arthritis treated with tocilizumab in the French Registry REGATE

2017-07-14

Abstract
Objectives
Observational studies have already reported the risk of serious infections in RA treated with tocilizumab, but in limited samples. The aim of this study was to investigate the predictive risk factors for serious infections in the largest European registry of patients treated with tocilizumab for RA.
Methods
A total of 1491 RA patients included in the French REGistry–RoAcTEmra were analysed to calculate the incidence rate of first serious infections rate after initiation of tocilizumab. To identify independent factors associated with serious infections, a Cox model was performed.
Results
Among the 1491 patients, average age 56.6 (13.6) years, 125 serious infections occurred in 122 patients (incidence rate of serious infection: 4.7/100 patient-years). Univariate analysis identified initial ACPA positivity as the only factor associated with a lower risk of serious infection [hazard ratio (HR) = 0.56, 95% CI: 0.36, 0.88]. Other factors significantly associated with a higher risk of serious infections were DAS28, concomitant Leflunomide (LEF) treatment, and absolute neutrophil count (ANC) at baseline. Initial ANC above 5.0 × 109/l (HR = 1.94, 95% CI: 1.32, 2.85; P < 0.001), negative ACPA (HR = 1.79, 95% CI: 1.15, 2.78; P = 0.012) at baseline and concomitant LEF treatment (LEF alone vs no treatment, HR = 2.18, 95% CI: 1.22, 3.88; P = 0.009) remained significantly associated with first serious infections in multivariate analysis after imputation for missing data.
Conclusion
The rate of first serious infections in current practice is similar to that reported in clinical trials. High ANC (above 5.0 × 109 at baseline), negative ACPA and concomitant therapy with LEF are predictive factors of serious infection, requiring in this case a tighter surveillance.



Rheumatoid arthritis patients with continued low disease activity have similar outcomes over 10 years, regardless of initial therapy

2017-07-13

Abstract
Objectives
To compare 10-year disease outcomes of RA patients who have continuous low disease activity and are on MTX with or without initial combination therapy with infliximab or prednisone and SSZ.
Methods
Recent-onset RA patients from the Behandel Strategieen (BeSt) (Dutch acronym for Treatment Strategies) study with 10 years of follow-up were analysed. Treatment was tightly controlled, targeted at DAS ⩽ 2.4. The selected patients had low disease activity from 6 months until 10 years and therefore did not intensify treatment. Patients were grouped into those receiving MTX monotherapy and those receiving initial combination therapy. Between-group differences over time were compared, using (generalized) linear mixed model analyses, for the outcomes DAS, HAQ, ESR, visual analogue scale patient global health, percentage of patients in (drug-free) remission and percentage of patients with Sharp/van der Heijde score progression ⩾5.
Results
At 10 years, 28/247 (11%) patients on MTX monotherapy (some tapered to drug free) had continued DAS ⩽ 2.4 compared with 68/261 (26%) patients on combination therapy (all tapered to monotherapy or drug free). No between-group differences in continuous responders were found over time, except for a higher percentage of patients in drug-free remission after MTX monotherapy. Significant group–time interactions were found for DAS, ESR and visual analogue scale patient global health, but the results seem clinically negligible.
Conclusion
More patients achieved continuous low disease activity on initial prednisone or infliximab combination therapy than on initial MTX monotherapy, but there appeared to be no additional benefits. Regardless of induction therapy, patients with continuous low disease activity have similar long-term outcomes, with only a higher proportion of patients in drug-free remission after MTX monotherapy.



Downregulation of miR-106b attenuates inflammatory responses and joint damage in collagen-induced arthritis

2017-07-06

Abstract
Objective
miRNAs are small, signal-strand, non-coding RNAs that function in post-transcriptional regulation. We analysed the in vivo effect of miR-106b (miR-106b-5p) on inflammatory bone loss in CIA mice.
Methods
CIA mice are developed by injecting DAB/1 mice with bovine type II collagen containing Freund’s adjuvant and then the in vivo effect of miR-106b is examined. On day 22, mice were given lentiviral negative control, lentiviral-mediated miR-106b mimics or lentiviral-mediated miR-106b inhibitor via orbital injection on a weekly basis. Morphological changes in the ankle joints were assessed via micro-CT and histopathology and cytokine expression levels were examined via immunohistochemical staining, ELISA or flow cytometric analysis. miR-106b and osteoclastic-related gene expression was evaluated via quantitative real-time PCR.
Results
CIA mice were found to have increased miR-106b expression and CIA-associated bone loss and inflammatory infiltration. miR-106b inhibitor treatment markedly decreased arthritis incidence and attenuated bone destruction and histological severity compared with the control group. Moreover, miR-106b inhibitor treatment suppressed RANK ligand (RANKL) expression, increased osteoprotegerin (OPG) expression and reduced the RANKL:OPG ratio in CIA mice. miR-106b inhibition also significantly decreased inflammatory mediator production in joint sections and reduced serum pro-inflammatory cytokine levels when compared with the control group. Additionally, miR-106b inhibition decreased tartrate-resistant acid phosphatase–positive cell numbers and suppressed murine bone marrow macrophage differentiation.
Conclusion
These findings indicate that miR-106b inhibition can ameliorate CIA-associated inflammation and bone destruction and thus may serve as a potential therapeutic for human RA treatment.



Reproducibility of capillaroscopic classifications of systemic sclerosis: results from the SCLEROCAP study

2017-07-04

Abstract
Objectives
Subgroups of capillaroscopic scleroderma landscape have been correlated with stages of SSc: two groups for Maricq’s classification (slow and active), and three for Cutolo’s classification (early, active and late). We report inter- and intra-observer agreement for these classifications as a preliminary step in the multicentre prospective SCLEROCAP study, which aims to assess the classification and single capillaroscopic items as prognostic tools for SSc.
Methods
SCLEROCAP included 385 patients. Agreement was studied in the first 100 patients, who were independently rated twice by two observers, blind to patients’ characteristics; 30 of the patients were rated once by six observers. After consensus meetings, these ratings were held again. Kappa and intraclass correlation coefficients were used to assess agreement.
Results
Interobserver agreement on 100 patients was moderate for Maricq and Cutolo classifications [κ 0.47 (0.28, 0.66) and 0.49 (0.33, 0.65), respectively], and became substantial after consensus meetings [0.64 (0.50, 0.77) and 0.69 (0.56, 0.81)]. Intra-observer agreement between two observers was moderate to substantial: κ 0.54 (0.33, 0.75) and 0.70 (0.57, 0.83) for Maricq’s classification; 0.57 (0.38, 0.77) and 0.76 (0.65, 0.87) for Cutolo’s. Thirty patients were rated once by each of six observers, and agreement was moderate to substantial: κ 0.57 ± 0.10 (Maricq) and 0.61 ± 0.12 (Cutolo). Agreement was substantial for bushy, giant capillaries and microhaemorrhages, moderate for capillary density and low for oedema, disorganization and avascular areas.
Conclusion
The moderate reproducibility of Maricq and Cutolo classifications might hamper their prognostic value in SSc patients. Consensus meetings improve reliability, a prerequisite for better prognostic performances. A focus on giant capillaries, haemorrhages and capillary density might be more reliable.



Disease activity dynamics in rheumatoid arthritis: patients’ self-assessment of disease activity via WebApp

2017-06-30

Abstract
Objectives
The aim was to evaluate patient self-assessment of RA disease activity in terms of Routine Assessment of Patient Index Data (RAPID) scores via a Web-based smartphone application (WebApp).
Methods
In this prospective, multicentre study, adult RA patients were examined by a rheumatologist at baseline and after 3 months. Patients were asked to complete WebApp questionnaires weekly. The time course of patient-assessed RAPID3/4 scores and their correlations with rheumatologist-assessed DAS28, as well as Clinical and Simplified Disease Activity Indices (CDAI/SDAI), were evaluated.
Results
Eighty patients were included in the analysis (median RA duration, 4.5 years; age, 57 years; 59% female). At baseline, there was a moderate to strong correlation between RAPID3 and DAS28 (r = 0.63), CDAI (r = 0.65) and SDAI (r = 0.61) scores. Similar or stronger correlations were seen at the 3-month follow-up visit (DAS28 r = 0.66, CDAI r = 0.71 and SDAI r = 0.61). Similar correlations were seen between RAPID4 and rheumatologist assessments. Correlations were not influenced by demographics or RA treatment. In the 3-month period, the RAPID3 score changed into a higher severity category than the category at baseline at least once in 47% of patients. When DAS28 scores were predicted from the RAPID3, 11% of patients had an increase of > 1 DAS28 unit during the 3-month observation period.
Conclusion
Web-based patient assessments were strongly correlated with rheumatologist assessments of RA activity and showed considerable variation during follow-up. This provides a rationale for further exploration of their use as cost-effective tools to monitor RA activity between outpatient visits and to optimize tight control strategies.



Enrichment of malondialdehyde–acetaldehyde antibody in the rheumatoid arthritis joint

2017-06-29

Abstract
Objective
To characterize the expression of malondialdehdye–acetaldehyde (MAA) adducts and anti-MAA antibody in articular tissues and serum of patients with RA.
Methods
Paired sera and SF were examined from 29 RA and 13 OA patients. Anti-MAA antibody, RF, ACPA and total immunoglobulin were quantified. SF-serum measures were compared within and between disease groups. The presence and co-localization of MAA, citrulline and select leukocyte antigens in RA and OA synovial tissues were examined using immunohistochemistry.
Results
Circulating and SF anti-MAA antibody concentrations were higher in RA vs OA by 1.5- to 5-fold. IgG (P < 0.001), IgM (P = 0.006) and IgA (P = 0.036) anti-MAA antibodies were higher in paired RA SF than serum, differences not observed for total immunoglobulin, RF or ACPA. In RA synovial tissues, co-localization of MAA with citrulline and CD19+ or CD27+ B cells was demonstrated and was much higher in magnitude than MAA or citrulline co-localization with T cells, monocytes, macrophages or dendritic cells (P < 0.01).
Conclusion
Anti-MAA antibodies are present in higher concentrations in the RA joint compared with sera, a finding not observed for other disease-related autoantibodies. Co-localization of MAA and citrulline with mature B cells, coupled with the local enrichment of anti-MAA immune responses, implicates MAA-adduct formation in local autoantibody production.









Using a reference when defining an abnormal MRI reduces false-positive MRI results—a longitudinal study in two cohorts at risk for rheumatoid arthritis

2017-06-27

Abstract
Objectives
The use of hand and foot MRI in the diagnostic process of RA has been advocated. Recent studies showed that MRI is helpful in predicting progression from clinically suspect arthralgia (CSA) to clinical arthritis, and from undifferentiated arthritis (UA) to RA. Symptom-free persons can also show inflammation on MRI. This study aimed to evaluate if MRI findings in symptom-free volunteers are relevant when defining a positive MRI.
Methods
Two hundred and twenty-five CSA patients and two hundred and one UA patients underwent MRI of MCP, wrist and MTP joints at baseline and were followed for 1 year on progression to arthritis and RA, respectively, as reported previously. MRI was considered positive if ⩾ 1 joint showed inflammation (called uncorrected definition), or if ⩾ 1 joint had inflammation that was present in < 5% of persons of the same age category at the same location (called 5% corrected definition). Test characteristics were compared for both definitions.
Results
By using MRI data of symptom-free volunteers as reference, specificity of MRI-detected inflammation increased from 22 to 56% in CSA patients, and from 10 to 36% in UA patients. The sensitivity was not affected; it was 88 and 85% in CSA patients and 93 and 93% in UA patients. The accuracy also increased, from 32 to 60% in CSA patients and 22 to 44% in UA patients.
Conclusion
The use of a reference population resulted in a substantial reduction of false-positive results, without influencing the sensitivity. Although common for other tests in medicine, this phenomenon is novel for MRI in the early detection of RA.



Cartilage improvement in a case of relapsing polychondritis

2017-06-26

A 64-year-old man visited us with a 10-week history of pain in both ears. After 5 weeks, he started noticing a feeling of bilateral aural fullness. Physical examination on presentation showed tenderness, swelling and redness of both ears. Episcleritis and oligoarthritis were also identified. The patient tested positive for anti–type II collagen antibody. Histopathological staining of a biopsy specimen of the auricular cartilage revealed destructive invasion of lymphocytes into the elastic cartilage, compatible with relapsing polychondritis. Symptoms resolved within a week after initiating moderate-dose glucocorticoid therapy. On review of the ears from 4 days to 6 months after starting therapy (Fig. 1: top row, right ear; bottom row, left ear), ear shape drooped, even after resolution of inflammation, but tended to improve over several months. Early identification and management may improve ear shape in relapsing polychondritis.



Increased autophagy contributes to the inflammatory phenotype of juvenile idiopathic arthritis synovial fluid T cells

2017-06-26

Abstract
Objectives
JIA is an autoimmune disease involving disturbed T-cell homeostasis, marked by highly activated effector T cells. Autophagy, a lysosomal degradation pathway, is crucial for maintaining cellular homeostasis by regulating the survival, differentiation and function of a large variety of cells, including T cells. The aim of this study was to examine the rate of autophagy in JIA T cells and to investigate the effect of inhibition of autophagy on the inflammatory phenotype of JIA T cells.
Methods
Autophagy-related gene expression was analysed in CD4+ T cells from the SF of JIA patients and healthy controls using RNA sequencing. Autophagy was measured by flow cytometry and western blot. The effect of inhibition of autophagy, using HCQ, on the cellular activation status was analysed using flow cytometry and multiplex immunoassay.
Results
Autophagy was increased in T cells derived from the site of inflammation compared with cells from the peripheral blood of patients and healthy controls. This increase in autophagy was not induced by JIA SF, but is more likely to be the result of increased cellular activation. Inhibition of autophagy reduced proliferation, cytokine production and activation marker expression of JIA SF-derived CD4+ T cells.
Conclusion
These data indicate that autophagy is increased in JIA SF-derived T cells and that targeting autophagy could be a promising therapeutic strategy to restore the disrupted T-cell homeostasis in JIA.



Life-threatening systemic capillary leak syndrome in juvenile dermatomyositis

2017-06-25

Rheumatology key message
  • Systemic capillary leak syndrome should be suspected in JDM patients with unexplained onset of oedema, myalgia, hypotension and rhabdomyolysis.



Chronic meningococcaemia—a medical oxymoron

2017-06-20

Rheumatology key message
  • Chronic meningococcaemia should be considered as a rare cause of recurrent fever, arthralgia and maculopapular rash.



Multicentric reticulohistiocytosis associated with thymic carcinoma

2017-06-14

A 70-year-old male presented with a 1-year history of bilateral hand, shoulder and knee pain. Examination revealed tenderness of the aforementioned joints without synovitis, as well as erythematous papules (Fig. 1A) on the hands, elbows and ears. Laboratory studies were normal, including full blood count, serum creatinine, ESR, CRP, ANA, RF and anti-CCP IgG. Hand radiographs (Fig. 1B) demonstrated erosive changes of the PIPs and DIPs. Biopsy of one papule (Fig. 1C) showed lymphohistiocytic proliferation and multinucleated giant cells with eosinophilic cytoplasm, confirming the diagnosis of multicentric reticulohistiocytosis. MTX therapy resulted in moderate symptom improvement.



Anti-NXP2 antibody-associated extensive subcutaneous calcinosis in adult-onset myositis

2017-06-12

A 68-year-old woman was followed since 1988 for DM. A combined therapy of corticosteroids and MTX controlled muscle involvement. In 1993, multiple subcutaneous nodules of calcinosis appeared on the limbs, chest and abdomen. In 2013, extensive calcinosis severely impaired the patient’s quality of life while myositis was under control (Fig 1). In 2016, a blood sample was collected in which circulating anti-NXP2 antibodies were detected.



Takayasu arteritis: active or not, that’s the question

2017-06-07

Rheumatology key message
  • With the current diagnostic tools it is difficult to assess disease activity in Takayasu arteritis.






Joan Agama Dellor 1977–2014

2017-05-11

Dr Joan Agama Dellor, a pioneering Ghanaian rheumatologist and BSR member, died prematurely at the age of 37 on 9 March 2014.



Primary angiitis of the central nervous system—a territory about to be discovered

2017-04-16

Primary angiitis of the CNS (PACNS) remains a major challenge for clinicians, and research has only been focused on this disease in the last few years. PACNS is rare, even among the already infrequent primary vasculitides, and it is probably not a single well-defined entity. Some forms affect the small vessels, and others merely the proximal larger vessels. Histology may reveal necrotizing or lymphocytic vasculitis, or granulomatous disease. This diversity of manifestations further complicates the diagnosis and management of patients with PACNS. Once the diagnosis is established, management of the disease is initiated analogous to treatment of the primary systemic vasculitides, that is, high-dose steroids, cyclophosphamide (CYC) and recently we find that Rituximab is being used for induction therapy. Outcomes following remission are still poorly documented.



Maintenance therapy is associated with better long-term outcomes in adult patients with primary angiitis of the central nervous system

2017-03-17

Abstract
Objective
We aimed to analyse the effect of maintenance therapy after induction on the outcomes of adult patients with primary angiitis of the CNS (PACNS).
Methods
We analysed long-term outcomes (relapse, survival and functional status) of patients enrolled in the French multicentre PACNS cohort who achieved remission after induction treatment and with ⩾12 months’ follow-up, according to whether or not they received maintenance therapy. Good outcome was defined as relapse-free survival and good functional status (modified Rankin scale ⩽ 2) at last follow-up.
Results
Ninety-seven patients [46 (47%) female, median age: 46 (18–78) years at diagnosis] were followed up for a median of 55 (5–198) months. Induction treatment consisted of glucocorticoids in 95 (98%) patients, combined with an immunosuppressant in 80 (83%) patients, mostly CYC. Maintenance therapy was prescribed in 48 (49%) patients, following CYC in 42 of them. Maintenance therapy was started 4 (3–18) months after glucocorticoid initiation. At last follow-up, good outcomes were observed in 32 (67%) patients who had received maintenance therapy vs 10 (20%) who had not (P < 0.0001). Thirty-two (33%) patients experienced relapse [10 (22%) had received maintenance therapy while 22 (45%) had not, P = 0.01]; four subsequently died from relapse. In the multivariate analysis, maintenance therapy was the only independent predictor of good outcome [odds ratio (OR) = 7.8 (95% CI: 3.21, 20.36), P < 0.0001].
Conclusion
The results of this long-term follow-up study suggest that maintenance therapy in adults with PACNS is associated with better functional outcomes and lower relapse rates. Further studies are needed to confirm these findings.



Value of multidisciplinary reassessment in attribution of neuropsychiatric events to systemic lupus erythematosus: prospective data from the Leiden NPSLE cohort

2017-02-28

Abstract
Objective
To determine the contribution of reassessment in the attribution process of neuropsychiatric (NP) events to SLE or other aetiologies in a large, prospective and multidisciplinary assessed NPSLE cohort and to compare these results with other available attribution models for NP events occurring in SLE.
Methods
Three hundred and four consecutive SLE patients presenting NP events were evaluated. All subjects underwent standardized multidisciplinary medical, neuropsychological, laboratory and radiological examination on the inclusion and reassessment dates. Diagnosis was always established by multidisciplinary consensus. The final diagnosis after reassessment also took into account disease course and response to treatment. These data were compared with currently available attribution models for NP events in SLE.
Results
A total of 463 NP events were established. After reassessment, attribution to SLE was discordant in 64 (13.8%) NP events when compared with the first visit. We show that 14.5% of NP events previously attributed to SLE reclassified as non-NPSLE. In 86.4% of these patients immunosuppressive therapy was started after the first visit. When reassessment and available attribution models were compared, NPSLE cases overlapped considerably. Although specificity was high for all comparisons (0.81–0.95), an important variation in sensitivity (0.39–0.83) and agreement estimates (κ = 0.29–0.68) was observed. The Italian algorithm showed the highest sensitivity and specificity (>0.80) and moderate agreement (0.59–0.64).
Conclusion
In clinical practice NP events presenting in SLE are too often attributed to an immune-mediated origin. Multidisciplinary reassessment avoids misclassification in NPSLE. Multidisciplinary reassessment is the reference standard in NP events presenting in SLE and cannot be replaced by available attribution models.



Type I interferon–mediated autoimmune diseases: pathogenesis, diagnosis and targeted therapy

2017-01-24

Abstract
Type I interferons (IFN-Is) are a group of molecules with pleiotropic effects on the immune system forming a crucial link between innate and adaptive immune responses. Apart from their important role in antiviral immunity, IFN-Is are increasingly recognized as key players in autoimmune CTDs such as SLE. Novel therapies that target IFN-I appear effective in SLE in early trials, but effectiveness is related to the presence of IFN-I biomarkers. IFN-I biomarkers may also act as positive or negative predictors of response to other biologics. Despite the high failure rate of clinical trials in SLE, subgroups of patients often respond better. Fully optimizing the potential of these agents is therefore likely to require stratification of patients using IFN-I and other biomarkers. This suggests the unified concept of type I IFN–mediated autoimmune diseases as a grouping including patients with a variety of different traditional diagnoses.



Is diffuse idiopathic skeletal hyperostosis a disease or a syndrome?

2016-12-24

Need for studies on angiogenesis-stimulating activity



Assessment and management of musculoskeletal disorders among patients living with HIV

2016-12-24

Abstract
HIV is a global pandemic. However, anti-retroviral therapy has transformed the prognosis and, providing compliance is good, a normal life expectancy can be anticipated. This has led to increasing numbers of people with chronic prevalent, treated infection living to older ages. Musculoskeletal pain is commonly reported by HIV patients and, with resumption of near-normal immune function, HIV-infected patients develop inflammatory rheumatic diseases that require assessment and management in rheumatology clinics. Moreover, it is becoming apparent that avascular necrosis and osteoporosis are common comorbidities of HIV. This review will contextualize the prevalence of musculoskeletal symptoms in HIV, informed by data from a UK-based clinic, and will discuss the management of active inflammatory rheumatic diseases among HIV-infected patients taking anti-retroviral therapy, highlighting known drug interactions.