Detection of inflammation by whole-body MRI in young people with juvenile idiopathic arthritis.

OBJECTIVES: To assess the frequency of joint inflammation detected by whole-body MRI (WBMRI) in young people (YP) with JIA and controls, and to determine the relationship between WBMRI-detected inflammation and clinical findings. METHODS: YP aged 14-24 years, with JIA (patients) or arthralgia without JIA (controls), recruited from one centre, underwent a WBMRI scan after formal clinical assessment. Consensus between at least two of the three independent radiologists was required to define inflammation and damage on WBMRI, according to predefined criteria. YP with JIA were deemed clinically active as per accepted definitions. The proportions of YP with positive WBMRI scans for joint inflammation (≥1 inflamed joint) as well as serum biomarkers were compared between active vs inactive JIA patients and controls. RESULTS: Forty-seven YP with JIA (25 active and 22 inactive patients) and 13 controls were included. WBMRI detected joint inflammation in 60% (28/47) patients with JIA vs 15% (2/13) controls (difference: 44%, 95% CI 20%, 68%). More active than inactive JIA patients had WBMRI-detected inflammation [76% (19/25) vs 41% (9/22), difference: 35% (95% CI 9%, 62%)], and this was associated with a specific biomarker signature. WBMRI identified inflammation in ≥ 1 clinically inactive joint in 23/47 (49%) patients (14/25 active vs 9/22 inactive JIA patients). CONCLUSIONS: WBMRI's validity in joint assessment was demonstrated by the higher frequency of inflammation in JIA patients vs controls, and in active vs inactive JIA patients. WBMRI found unsuspected joint inflammation in 49% YP with JIA, which needs further investigation of potential clinical implications.

A simple, clinically usable whole-body MRI system of joint assessment in adolescents and young people with juvenile idiopathic arthritis.

OBJECTIVES: To introduce and evaluate a simple method for assessing joint inflammation and structural damage on whole-body MRI (WBMRI) in juvenile idiopathic arthritis (JIA), which is usable in clinical practice. METHODS: The proposed system utilises post-contrast Dixon WBMRI scans. Joints are assessed for synovitis (grade 0-2) and structural damage (present/absent) at 81 sites. The synovitis grading is based on features including above-normal intensity synovial enhancement, synovial hypertrophy, joint effusion, subarticular bone marrow oedema and peri-articular soft tissue oedema.This system was evaluated in a prospective study of 60 young people (47 patients with JIA and 13 controls with non-inflammatory musculoskeletal pain) who underwent a WBMRI. Three readers (blinded to diagnosis) independently reviewed all images and re-reviewed 20 individual scans. The intra- and inter-reader overall agreement (OA) and the intra- and inter-reader Gwet's agreement coefficients 2 (GAC2) were measured for the detection of a) participants with ≥1 joint with inflammation or structural damage and b) joint inflammation or structural damage for each joint. RESULTS: The inter-reader OA for detecting patients with ≥1 joint with inflammation, defined as grade 2 synovitis (G2), and ≥1 joint with structural damage were 80% and 73%, respectively. The intra-reader OA for readers 1-3 were 80-90% and 75-90% respectively. The inter-reader OA and GAC2 for joint inflammation (G2) at each joint were both ≥85% for all joints but were lower if grade 1 synovitis was included as positive. CONCLUSION: The intra- and inter-reader agreements of this WBMRI assessment system are adequate for assessing objective joint inflammation and damage in JIA.

Histographic analysis of oedema and fat in inflamed bone marrow based on quantitative MRI.

OBJECTIVE: To demonstrate proof-of-concept for a quantitative MRI method using histographic analysis to assess bone marrow oedema and fat metaplasia in the sacroiliac joints. MATERIALS AND METHODS: Fifty-three adolescents aged 12-23 with known or suspected sacroiliitis were prospectively recruited and underwent quantitative MRI (qMRI) scans, consisting of chemical shift-encoded (at 3 T) and diffusion-weighted imaging (at 1.5 T), plus conventional MRI (at 1.5 T) and clinical assessment. qMRI scans produced proton-density fat fraction (PDFF) and apparent diffusion coefficient (ADC) maps of the sacroiliac joints (SIJs), which were analysed using an in-house software tool enabling partially automated ROI definition and histographic analysis. Logistic regression and receiver operating characteristic (ROC) analyses assessed the predictive performance of ADC- and PDFF-based parameters in identifying active inflammation (oedema) and structural damage (fat metaplasia). RESULTS: ADC-based parameters were associated with increased odds of oedema (all p < 0.05); ROC-AUC was higher for histographic parameters representing the upper end of the ADC distribution than for simple averages. Similarly, PDFF-based parameters were associated with increased odds of fat metaplasia (all p < 0.05); ROC area-under-the-curve was higher for histographic parameters representing the upper end of the PDFF distribution than for simple averages. Both ADC- and PDFF-based histographic parameters demonstrated excellent inter- and intra-observer agreement (ICC > 0.9). CONCLUSIONS: ADC-based parameters can differentiate patients with bone marrow oedema from those without, whilst PDFF-based parameters can differentiate patients with fat metaplasia from those without. Histographic analysis might improve performance compared with simple averages such as the mean and median and offers excellent agreement within and between observers. KEY POINTS: • Quantitative MRI with histographic analysis can identify bone marrow oedema (an active inflammatory lesion) and fat metaplasia (a 'chronic' inflammatory lesion) in patients with spondyloarthritis. • The use of histographic analysis might improve the performance of quantitative MRI for detecting bone marrow oedema and fat metaplasia compared with simple averages such as the mean and median. • Bone marrow oedema and fat metaplasia are known to be of diagnostic and prognostic significance, and the proposed method could support clinical decisions around biologic (and other) therapies in spondyloarthritis.

Depressive symptoms, pain and disability for adolescent patients with juvenile idiopathic arthritis: results from the Childhood Arthritis Prospective Study.

Objectives: To determine if depressive symptoms assessed near diagnosis associate with future measures of pain, disability and disease for adolescent patients diagnosed with JIA. Methods: Data were analysed from JIA patients aged 11-16 years recruited to the Childhood Arthritis Prospective Study, a UK-based inception cohort of childhood-onset arthritis. Depressive symptoms (using the Mood and Feelings Questionnaire; MFQ), active and limited joint count, disability score (Childhood Health Assessment Questionnaire), pain visual analogue scale and patient's general evaluation visual analogue scale were collected. Associations between baseline measures (first visit to paediatric rheumatologist) were analysed using multiple linear regression. Linear mixed-effect models for change in the clinical measures of disease over 48 months were estimated including MFQ as an explanatory variable. Results: Data from 102 patients were analysed. At baseline, median (IQR) age was 13.2 years (11.9-14.2 years) and 14.7% scored over the MFQ cut-off for major depressive disorder. At baseline, depressive symptoms significantly associated with all clinical measures of disease (P ⩽ 0.01). High baseline depressive symptoms scores predicted worse pain (P ⩽ 0.005) and disability (P ⩽ 0.001) 12 months later but not active and limited joint counts. Conclusions: Adolescent patients with JIA and depressive symptoms had more active joints, pain and disability at the time of their first specialist appointment. The associations between baseline depression and both pain and disability continued for at least one year, however, this was not the case for active joint count.

Diffusion-weighted imaging is a sensitive biomarker of response to biologic therapy in enthesitis-related arthritis.

Objective: The aim was to evaluate diffusion-weighted imaging (DWI) as a tool for measuring treatment response in adolescents with enthesitis-related arthropathy (ERA). Methods: Twenty-two adolescents with ERA underwent routine MRI and DWI before and after TNF inhibitor therapy. Each patient's images were visually scored by two radiologists using the Spondyloarthritis Research Consortium of Canada system, and sacroiliac joint apparent diffusion coefficient (ADC) and normalized ADC (nADC) were measured for each patient. Therapeutic clinical response was defined as an improvement of ⩾ 30% physician global assessment and radiological response defined as ⩾ 2.5-point reduction in Spondyloarthritis Research Consortium of Canada score. We compared ADC and nADC changes in responders and non-responders using the Mann-Whitney-Wilcoxon test. Results: For both radiological and clinical definitions of response, reductions in ADC and nADC after treatment were greater in responders than in non-responders (for radiological response: ADC: P < 0.01; nADC: P = 0.055; for clinical response: ADC: P = 0.33; nADC: P = 0.089). ADC and nADC could predict radiological response with a high level of sensitivity and specificity and were moderately sensitive and specific predictors of clinical response (the area under the receiver operating characteristic curves were as follows: ADC: 0.97, nADC: 0.82 for radiological response; and ADC: 0.67, nADC: 0.78 for clinical response). Conclusion: DWI measurements reflect the response to TNF inhibitor treatment in ERA patients with sacroiliitis as defined using radiological criteria and may also reflect clinical response. DWI is more objective than visual scoring and has the potential to be automated. ADC/nADC could be used as biomarkers of sacroiliitis in the clinic and in clinical trials.

Association of the apparent diffusion coefficient with maturity in adolescent sacroiliac joints.

PURPOSE: To determine the extent to which apparent diffusion coefficient (ADC) values vary with skeletal maturity in adolescent joints. MATERIALS AND METHODS: A retrospective study was performed with Institutional Review Board (IRB) approval. We used a picture archiving and communication system (PACS) search to identify and recruit all adolescents who had undergone 1.5T magnetic resonance imaging (MRI) of the sacroiliac joints (SIJs) between January 2010 and June 2015, and had no evidence of sacroiliitis and normal inflammatory markers. In all, 55 individuals were assessed. For each patient, coronal and sagittal images of the sacrum were visually analyzed to determine sacral maturity. Patients were divided into three groups depending on the degree of fusion of the sacral segmental apophyses: "Fused," "Partial," and "Unfused." For each group, SIJ ADC was measured using a linear region-of-interest technique. RESULTS: Mean ADC values were 690 × 10(-6) mm(2) /s in the fused group, 720 × 10(-6) mm(2) /s in the partial group, and 842 × 10(-6) mm(2) /s in the unfused group. ADC values were significantly higher in the unfused group than in the fused group (P = 0.046). ADC values were also higher in unfused subjects than partially fused subjects (P = 0.074). CONCLUSION: Joint ADC values are higher in skeletally immature (unfused) patients than in skeletally more mature (fused) patients. ADC values measured in the unfused group overlap with those previously reported in sacroiliitis. These results suggest that ADC measurements in adolescent joints must be interpreted in light of joint maturity. Joint immaturity may lead to misdiagnosis of sacroiliitis, since immature juxta-articular bone may appear similar to inflammation. J. Magn. Reson. Imaging 2016. J. Magn. Reson. Imaging 2016;44:556-564.

Feasibility and acceptability of multidisciplinary team training in health coaching: Case study in adolescent rheumatology.

The central importance of the biopsychosocial model of chronic disease is increasingly recognised in the management of long-term conditions (LTC), which are often associated with chronic pain, fatigue and disability. Despite the physical and mental health impact, 'struggle' to maintain self-efficacy, gap in effective transition to adult pathways and long term consequences of poor disease control and lifestyle choices in young people with LTCs, innovation in this age range is rarely reported in generic journals. This paper explores the feasibility and acceptability of health coaching with young service users to increase engagement and self-management, achieved through multidisciplinary team (MDT) training in Adolescent Rheumatology.

Management of refractory disease and persistent symptoms in inflammatory arthritis: qualitative framework analysis of interviews with patients and healthcare professionals.

Objectives: This study aims to explore patients' and clinicians' experiences in managing and living with refractory disease (RD) and persistent physical and emotional symptoms (PPES) in patients with RA or polyarticular JIA from their perspectives through interviews and/or focus groups. Methods: A qualitative exploration with 25 patients and 32 multidisciplinary rheumatology healthcare professionals (HCPs) was conducted to obtain participants respective understanding and experiences of managing RD/PPES and its impact on the patient-professional relationship. A pragmatic epistemology approach with framework analysis was employed. Results: Four key themes were identified from both patients and professionals in the management of RD/PPES: risk/perpetuating factors/triggers; need for a patient-centred holistic approach to care, diagnosis and treatment; discordance and impact on the patient-practitioner relationship and current problems in managing RD/PPES. These themes covered 22 subthemes, with none being patient specific and seven being HCP specific. Suggestions for potential management strategies were highlighted throughout, such as involving other specialties or a multidisciplinary team, assessing/treating patient-reported outcome measures and psychosocial factors, patient (re)education, need for adjustments/aids or adaptations, checking the diagnosis and further investigations/imaging and optimizing medications. Conclusion: Management strategies need to be developed that enable appropriate treatment plans for those with RD/PPES that account for wider biopsychosocial factors beyond inflammation and reduce discordance in the patient-practitioner relationship.

Prevalence of chronic pain or analgesic use in children and young people and its long-term impact on substance misuse, mental illness, and prescription opioid use: a retrospective longitudinal cohort study.

Background: Epidemiological studies suggest chronic and recurrent pain affects around a quarter of children, while 8% report intense and frequent pain. The long-term implications of chronic pain in childhood are uncertain. Using electronic health records (EHRs) we used both disease codes and medicines prescription records to investigate the scale of chronic pain and long-term analgesic use in children and young people (CYP), and if chronic pain and/or use of analgesic medicines at an early age is associated with substance misuse, use of prescription opioids, and poor mental health in adulthood. Methods: We conducted a cohort study using data from IQVIA Medical Research Data UK. We identified individuals aged 2-24 with exposure to either a diagnostic code indicating chronic pain (diagnosis-exposed), repeat prescription for medicines commonly used to treat pain (prescription-exposed), or both. Follow-up began at 25, and the unexposed population acted as comparators. We calculated hazard ratios (HR) for mental health and substance misuse outcomes, and rate ratios (RR) for opioid prescriptions in adulthood. Additionally, we investigated which diagnoses, if any, were over-represented in the prescription-exposed subgroup. Findings: The cohort constituted 853,625 individuals; 146,431 had one or more of the exposures of interest (diagnosis-exposed = 115,101, prescription-exposed = 20,298, both-exposed = 11,032), leaving 707,194 as comparators. Median age at index exposure was 18.7 years (IQR 14.7-22.3). On average during follow-up, the pooled exposed group had, respectively, a 31% and 17% higher risk of adverse mental health and substance misuse outcomes (adjusted HR [95% CI] of 1.31 [1.29-1.32] and 1.17 [1.11-1.24]). Exposed individuals also received prescription opioids at double the rate of unexposed individuals on average during follow-up (adjusted RR 2.01 [95% CI 1.95-2.10]). Outcomes varied between exposure subgroups, with prescription- and both-exposure tending to have worse outcomes. Unlike these two subgroups, in the diagnosis-exposed subgroup we did not detect a greater risk of substance misuse. Interpretation: Chronic pain in CYP is associated with increased prescription opioid use and adverse mental health outcomes in adulthood, as is repeat prescription for analgesic medicines, but only the latter is also associated with substance misuse in adulthood. It is essential to avoid the harms of under-treating pain in CYP while giving due consideration to the risks posed by analgesic medicines. Early recognition of chronic pain in CYP and utilising non-pharmacological management options may help minimise overprescribing, and long-term reliance on dependence-forming-drugs. Funding: AL is an NIHR funded academic clinical fellow, and was supported by funding from UCLH Charities while carrying out this work. RS and DS are part of the Advanced Pain Discovery Platform and were supported by a UKRI and Versus Arthritis grant (MR/W002566/1) as part of the Consortium Against Pain Inequality. AW was supported by the Wellcome Trust (220558/Z/20/Z).

The role of whole-body MRI in musculoskeletal inflammation detection and treatment response evaluation in inflammatory arthritis across age: A systematic review.

OBJECTIVE: To evaluate the relation between whole-body MRI (WBMRI) outcomes and disease activity measures, including clinical examination, composite scores, and other imaging outcomes, and the ability of WBMRI to detect treatment response in patients with inflammatory arthritis (IA) across age. METHODS: Human studies published as full text or abstract in the PubMed and MEDLINE and Cochrane databases from inception to 11th April 2021 were systematically and independently searched by two reviewers. Studies including patients with rheumatoid arthritis (RA), psoriatic arthritis (PsA), spondyloarthritis (SpA), juvenile idiopathic arthritis (JIA) or unclassified inflammatory arthritis (UA) who underwent WBMRI and which reported on disease outcomes were included. RESULTS: Nineteen full-text studies were eligible for inclusion: 2 interventional, 7 retrospective and 10 prospective observational studies, comprising 540 participants (SpA 38.7%, RA 24.8%, JIA 17.8%, PsA 11.5%, healthy controls 5.9%, UA 1.3%). Abstracts of 6 conference papers were reported separately. Five studies in PsA and SpA and 4 in RA measured the frequency of WBMRI-detected and clinically-detected synovitis, and all found the former to be more frequent. Less enthesitis was detected by WBMRI than clinical examination in 5/8 studies. After biologic treatment, the WBMRI inflammation scores declined in 3 studies in SpA and 2 in RA, whilst in 3 studies the results were equivocal. CONCLUSION: The ability of WBMRI to assess disease activity and treatment response in IA was adequate overall. Further studies are needed to corroborate WBMRI findings with IA outcomes and investigate the clinical value of subclinical inflammation.

Adalimumab or etanercept as first line biologic therapy in enthesitis related arthritis (ERA) - a drug-survival single centre study spanning 10 years.

OBJECTIVES: To analyse and compare drug-survival of adalimumab and etanercept (and their biosimilars) in biologic-naïve patients with ERA (Enthesitis-Related Arthritis). METHODS: In this retrospective observational study, conventional statistics and machine-learning were applied to compare drug-survival (adalimumab, etanercept and their biosimilars initiated: 2009-2019) in ERA and identify determinants. The primary outcome was discontinuation of treatment due to primary- or secondary-failure and adverse drug-reactions. RESULTS: During the observation period, 99 of 188 patients with ERA on first-line TNF inhibitors (etanercept-n=108, adalimumab-n=80) discontinued their treatment (median survival-time 3.9years, 95%CI 2.6-4.9years). Adalimumab was associated with longer drug-survival compared to etanercept especially after an initial positive response, with the median time to treatment discontinuation 4.9years (95% CI 3.9-5.7) for adalimumab, compared to 2years (95%CI 1.4-4.0) for etanercept (HR of treatment-discontinuation-0.49, 95%CI 0.32--0.75, p=0.001). Adjusted by propensity-score, adalimumab-methotrexate combination was associated with longer drug survival, compared to adalimumab-monotherapy (HR-0.41, 95%CI 0.20-0.85), etanercept-monotherapy (HR-0.28, 95%CI 0.15-0.53), and etanercept-methotrexate combination (HR-0.39, 95%CI 0.21-0.73). The presence of HLA-B27 was associated with longer drug-survival (HR-0.50, 95%CI 0.29-0.87) following an initial positive response. Higher-CRP at baseline was associated with higher rate of primary-failure (HR-1.68, 95%CI 1.08-2.62). Axial-ERA (sacroiliitis±spinal-involvement) was associated with poorer drug-survival for both primary- and secondary-failure (overall HR-2.03, 95%CI 1.22-3.40). Adjusted by propensity-score, shorter drug-survival was observed in patients with baseline-CRP≥12.15 mg/L, but only in the context of axial-ERA, not in peripheral-ERA (no sacroiliitis/spinal-involvement) (HR-2.28, 95%CI 1.13--3.64). CONCLUSION: Following an initial positive primary response, continuing methotrexate with adalimumab was associated with the longest drug-survival compared to adalimumab-monotherapy or etanercept-based regimens. Axial-ERA was associated with a poorer drug-survival. A CRP >12.15 in patients with axial-ERA was associated with a higher rate of primary-failure. Further prospective studies are required to confirm these findings.

Relationship between ethnicity and multidisciplinary intervention for young people with rheumatic and musculoskeletal diseases.

Introduction: There is growing recognition of the impact of societal factors on health throughout a patient's lifespan. The COVID-19 pandemic has exposed the impact of racial disparity on health outcomes. Aims: We aimed to investigate the association between ethnicity and the multidisciplinary team (MDT) interventions for young people (YP) with complex care needs. Method: This retrospective, single-centre, cross-sectional study was conducted within the department of adolescent and young adult rheumatology at University College Hospital, London, between August 2019 and August 2021. We extracted demographic, clinical and laboratory data. The index of multiple deprivation was extracted from the Office for National Statistics database. R software was used for analysis. Results: We identified 310 YP referred to the MDT with a median age of 18 years (interquartile range 17-19). The female patient to male patient ratio was 2.4. Over a third of our cohort were from deprived areas. Comparison between Black, Asian and minority ethnic (BAME) and White ethnic groups revealed significant differences in terms of referral for pain optimisation (p=0.006), social support (p<0.00001), and adherence and non-clinic attendance (p=0.0004). Conclusion: Our findings reveal the importance of quality data for early identification and support of vulnerable YP, particularly those from BAME communities.

Similarities and Differences Between Juvenile and Adult Spondyloarthropathies.

Spondyloarthritis (SpA) encompasses a broad spectrum of conditions occurring from childhood to middle age. Key features of SpA include axial and peripheral arthritis, enthesitis, extra-articular manifestations, and a strong association with HLA-B27. These features are common across the ages but there are important differences between juvenile and adult onset disease. Juvenile SpA predominantly affects the peripheral joints and the incidence of axial arthritis increases with age. Enthesitis is important in early disease. This review article highlights the similarities and differences between juvenile and adult SpA including classification, pathogenesis, clinical features, imaging, therapeutic strategies, and disease outcomes. In addition, the impact of the biological transition from childhood to adulthood is explored including the importance of musculoskeletal and immunological maturation. We discuss how the changes associated with adolescence may be important in explaining age-related differences in the clinical phenotype between juvenile and adult SpA and their implications for the treatment of juvenile SpA.

Association of Anxiety With Pain and Disability but Not With Increased Measures of Inflammation in Adolescent Patients With Juvenile Idiopathic Arthritis.

OBJECTIVE: To explore whether anxiety and depression are associated with clinical measures of disease for adolescent patients with juvenile idiopathic arthritis (JIA) and whether anxiety and depression are associated with increased peripheral proinflammatory cytokine levels in adolescent patients with JIA and in healthy adolescent controls. METHODS: A total of 136 patients with JIA and 88 healthy controls ages 13-18 years completed questionnaires on anxiety and depressive symptoms. For patients with JIA, pain, disability, physician global assessment (using a visual analog scale [VAS]), and number of joints with active inflammation (active joint count) were recorded. In a subsample, we assessed lipopolysaccharide-stimulated interleukin 6 (IL-6) production from peripheral blood mononuclear cells, serum IL-6, cortisol, and C-reactive protein levels. Data were analyzed by linear regression analysis. RESULTS: Levels of anxiety and depressive symptoms in patients with JIA were not significantly different than those in healthy controls. For patients with JIA, anxiety was significantly associated with disability (ß = 0.009, P = 0.002), pain (ß = 0.029, P = 0.011), and physician global assessment VAS (ß = 0.019, P = 0.012), but not with active joint count (ß = 0.014, P = 0.120). Anxiety was not associated with any laboratory measures of inflammation for JIA patients. These relationships were also true for depressive symptoms. For healthy controls, there was a trend toward an association of anxiety (but not depressive symptoms) with stimulated IL-6 (ß = 0.004, P = 0.052). CONCLUSION: Adolescent patients with JIA experience equivalent levels of anxiety and depressive symptoms as healthy adolescents. For adolescent patients with JIA, anxiety and depressive symptoms are associated with pain, disability, and physician global assessment VAS, but not with inflammation.

The pain trajectory of juvenile idiopathic arthritis (JIA): translating from adolescent patient report to behavioural sensitivity in a juvenile animal model.

BACKGROUND: While pain is a common symptom in JIA patients, it remains unclear why some JIA patients develop ongoing or persistent pain. Complex clinical and social settings confound analysis of individual factors that may contribute to this pain. To address this, we first undertook a retrospective analysis of pain reports in a JIA patient cohort with the aim of identifying potential factors contributing to persistent pain. We then carried out an experimental laboratory study, using joint inflammatory pain behaviour in rodents, to validate the role of these factors in the onset of persistent pain under controlled conditions. METHODS: Patients: Retrospective analysis of anonymised pain visual analogue scale (VAS) scores and accompanying clinical scores from 97 JIA patients aged 13-19 (mean: 16.40 ± 1.21) collected over 50 weeks. Rats: Experimental study of pain behaviour following intra-articular microinjection of complete Freund's adjuvant (CFA) in adolescents (n = 25) and young adults (n = 43). Some animals (n = 21) had been previously exposed to joint inflammation in infancy or adolescence. RESULTS: Patients: Cluster analysis of patient pain VAS scores revealed three trajectories over 50 weeks: consistently low pain (n = 45), variable pain (n = 30) and persistently high pain (n = 22). Number of actively inflamed joints did not differ in the three groups. High pain at a single visit correlated with greater physician global assessment of disease activity, while a high pain trajectory over 50 weeks was associated with more limited joints but fewer actively inflamed joints. Rats: Rodents administered ankle joint CFA also exhibit low, medium and high joint pain sensitivities, independent of joint inflammation. Prolonged inflammatory pain behaviour was associated with high background pain sensitivity, following joint inflammation at an earlier stage in life. CONCLUSIONS: Both JIA patients and rodents differ in their individual pain sensitivity independent of the concurrent joint inflammation. Using experimental animal models allows us to isolate physiological factors underlying these differences, independently of social or clinical factors. The results suggest that a history of prior arthritic activity/joint inflammation may contribute to high pain sensitivity in adolescents with JIA.

Sacroiliac Joint Ankylosis in Young Spondyloarthritis Patients Receiving Biologic Therapy: Observation of Serial Magnetic Resonance Imaging Scans.

OBJECTIVE: To assess the temporal relationship between initiating biologic therapy and magnetic resonance imaging (MRI) scores of inflammation and structural damage in young patients with spondyloarthritis. METHODS: A local adolescent/young adult patient rheumatology database was searched for patients ages 12-24 years who had evidence of sacroiliitis on MRI and a clinical diagnosis of enthesitis-related arthritis (ERA) with axial involvement or nonradiographic axial spondyloarthritis. Patients treated with tumor necrosis factor inhibitor (TNFi) therapy who had undergone a minimum of 1 MRI scan before and 2 MRI scans after starting TNFi therapy (over ≥2 years) were included. Images of the sacroiliac joints were scored for inflammation and structural abnormalities (including erosions, fat metaplasia, and fusion). The effects of TNFi therapy and of time since initiation of TNFi therapy on inflammation and structural abnormalities were assessed using a mixed-effects regression analysis. RESULTS: Twenty-nine patients (ages 12-23 years) with ERA or nonradiographic axial spondyloarthritis who underwent TNFi therapy were included. Inflammation scores were significantly lower in patients receiving TNFi treatment (P = 0.013), but there was no significant effect of time from TNFi initiation on inflammation (P = 0.125). Conversely, there was no significant effect of active TNFi treatment on fusion scores (P = 0.308), but fusion scores significantly increased with time from TNFi initiation (P < 0.001); a similar positive relationship between time since biologic start and fat metaplasia scores was observed. CONCLUSION: TNFi therapy failed to prevent the eventual development of joint ankylosis in this cohort of young patients with spondyloarthritis, despite a substantial reduction in inflammation with TNFi therapy.

Development of a benchmarking toolkit for adolescent and young adult rheumatology services (BeTAR).

BACKGROUND: Young people (YP; 12-24 years old) with rheumatic diseases face many challenges associated with chronic illness in addition to the physiological and psychosocial changes of adolescence. Timely access to developmentally appropriate multidisciplinary care is key to successfully managing rheumatic diseases, but gaps in the care of this vulnerable age group still exist. This study aimed to develop a benchmarking toolkit to enable comparative evaluation of YP rheumatology services in order to promote best practice and reduce variations in service delivery. METHODS: A staged and consultative method was used across a broad group of stakeholders in the UK (YP, parents/other carers, and healthcare professionals, HCPs) to develop this toolkit, with reference to pre-existing standards of YP-friendly healthcare. Eighty-seven YP (median age 19 years, range 12-24 years) and 26 rheumatology HCPs with 1-34 years of experience caring for YP have participated. RESULTS: Thirty quality criteria were identified, which were grouped into four main domains: assessment and treatment, information and involvement, accessibility and environment, and continuity of care. Two toolkit versions, one to be completed by HCPs and one to be completed by patients, were developed. These were further refined by relevant groups and face validity was confirmed. CONCLUSIONS: A toolkit has been developed to systematically evaluate and benchmark YP rheumatology services, which is key in setting standards of care, identifying targets for improvement and facilitating research. Engagement from YP, clinical teams, and commissioners with this tool should facilitate investigation of variability in levels of care and drive quality improvement.

Articular presentation of disseminated histoplasmosis.

Histoplasmosis is an important opportunistic disease to consider in immunocompromised patients from endemic areas. Articular presentations of disseminated histoplasmosis are uncommon. We describe the case of a renal transplant recipient originating from South Africa in whom a suppurative arthritis presented as a manifestation of disseminated histoplasmosis.

Microscopic polyangiitis and myasthenia gravis: the battle of Occam and Hickam.

Microscopic polyangiitis (MPA) is a pauci-immune, necrotising, small-vessel vasculitis with an incidence of 3.6 per million population that typically presents in adulthood. Myasthenia gravis (MG), the most common disorder of the neuromuscular junction is rare, with an incidence of four per million population. We present the case of an adolescent girl previously diagnosed with MPA at age 7 years who presented with breathlessness and respiratory failure aged 15 years. The respiratory symptoms were due to thymoma-MG, which was successfully treated with cholinesterase inhibitors and thymectomy. This case report illustrates that the well-established doctrines of Occam's razor and of 'common conditions occurring commonly' are not universally applicable, and that in the adolescent age group, one should still consider Hickam's dictum.