Kate Armon

Disease activity, severity, and damage in the UK juvenile-onset systemic lupus erythematosus cohort

OBJECTIVE The UK Juvenile-Onset Systemic Lupus Erythematosus (JSLE) Cohort Study is a multicenter collaborative network established with the aim of improving the understanding of juvenile SLE. The present study was undertaken to describe the clinical manifestations and disease course in patients with juvenile SLE from this large, national inception cohort. METHODS Detailed data on clinical phenotype were collected at baseline and at regular clinic reviews and annual followup assessments in 232 patients from 14 centers across the UK over 4.5 years. Patients with SLE were identified according to the American College of Rheumatology (ACR) SLE classification criteria. The present cohort comprised children with juvenile SLE (n=198) whose diagnosis fulfilled ≥4 of the ACR criteria for SLE. RESULTS Among patients with juvenile SLE, the female:male sex distribution was 5.6:1 and the median age at diagnosis was 12.6 years (interquartile range 10.4-14.5 years). Male patients were younger than female patients (P<0.01). Standardized ethnicity data demonstrated a greater risk of juvenile SLE in non-Caucasian UK patients (P<0.05). Scores on the pediatric adaptation of the 2004 British Isles Lupus Assessment Group disease activity index demonstrated significantly increased frequencies of musculoskeletal (82%), renal (80%), hematologic (91%), immunologic (54%), and neurologic (26%) involvement among the patients over time. A large proportion of the patients (93%) were taking steroids and 24% of the patients required treatment with cyclophosphamide. Disease damage was common, with 28% of the patients having a Systemic Lupus International Collaborating Clinics/ACR damage score of ≥1. CONCLUSION The data on these patients from the UK JSLE Cohort Study, comprising one of the largest national inception cohorts of patients with juvenile SLE to date, indicate that severe organ involvement and significant disease activity are primary characteristics in children with juvenile SLE. In addition, accumulation of disease-associated damage could be seen.

The relationship between benign joint hypermobility syndrome and psychological distress: a systematic review and meta-analysis

OBJECTIVE This study examines the reported evidence of an association between benign joint hypermobility syndrome (BJHS) and psychological symptoms. METHODS A systematic review of published (AMED, CINAHL, MEDLINE, EMBASE, PubMed, Cochrane Library) and unpublished research databases (OpenGrey, the World Health Organization (WHO) International Clinical Trials Registry Platform, Current Controlled Trials, the UK National Research Register Archive) was performed from their inception to January 2013. Studies assessing the prevalence and incidence of psychological conditions for people diagnosed with BJHS were included. Meta-analysis assessing the odds ratio (OR) and standardized mean difference in severity of psychological conditions was performed. Methodological quality was assessed using the Critical Appraisal Skills Programme (CASP) appraisal tools. RESULTS Fourteen papers including 3957 participants, 1006 people with and 2951 controls without BJHS were eligible. The overall methodological quality was moderate. The results indicated that people with BJHS experience significantly greater perceptions of fear and more intense fear (P < 0.05) and have a higher probability of demonstrating agoraphobia (P < 0.05), anxiety (OR 4.39, 95% CI 1.92, 10.40), depression (OR 4.10, 95% CI 1.79, 9.41) and panic disorders (OR 6.72, 95% CI 2.22, 20.35) than those without BJHS (P ≤ 0.005). Neither anxiety nor depression have been assessed in childhood populations. CONCLUSION People with BJHS commonly exhibit a range of symptoms related to anxiety and depression. Considerable emotional symptoms accompany BJHS. Further study is warranted to explore how these results relate to non-Mediterranean populations and children. However, the data suggest that targeting psychological symptoms could be an important approach to managing the range of symptoms reported in these patients.

Physiotherapy and occupational therapy interventions for people with benign joint hypermobility syndrome: a systematic review of clinical trials

Abstract Purpose: This study assessed the literature to determine the efficacy and effectiveness of physiotherapy and occupational therapy interventions in the treatment of people with benign joint hypermobility syndrome (BJHS). Methods: Published literature databases including: AMED, CINAHL, MEDLINE, EMBASE, PubMed and the Cochrane Library, in addition to unpublished databases and trial registries were searched to October 2012. All clinical trials comparing the clinical outcomes of Occupational Therapy and Physiotherapy interventions compared to non-treatment or control intervention for people with BJHS were included. Results: Of the 126 search results, 3 clinical studies satisfied the eligibility criteria. The data provides limited support for the use of wrist/hand splints for school children. While there is some support for exercise-based intervention, there is insufficient research to determine the optimal mode, frequency, dosage or type of exercise which should be delivered. Conclusions: The current evidence-base surrounding Occupational Therapy and Physiotherapy in the management of BJHS is limited in size and quality. There is insufficient research exploring the clinical outcomes of a number of interventions including sensory integration, positioning and posture management and education. Longer term, rigorous multi-centre randomised controlled trials are warranted to begin to assess the clinical and cost-effectiveness of interventions for children and adults with BJHS. Implications for Rehabilitation There is an evidence-base to support clinician’s use of proprioceptive-based exercises in adults, and either tailored or generalised physiotherapy regimes for children with BJHS. Clinicians should be cautious when considering the prescription of hand/wrist splints for school age children with BJHS, based on the current research. Until further multi-centre trials are conducted assessing the clinical and cost-effectiveness of interventions for children and adult with BJHS, clinical decision-making should be based on theoretical rather than evidence-based grounds for this population.

Mucocutaneous manifestations in a UK national cohort of juvenile-onset systemic lupus erythematosus patients

OBJECTIVE To determine whether mucocutaneous manifestations are associated with major organ involvement in a UK national cohort of juvenile-onset SLE (JSLE) patients. METHODS JSLE patients (n = 241) from 15 different centres whose diagnosis fulfilled four or more of the ACR criteria were divided into two groups: those with at least one ACR mucocutaneous criterion (ACR skin feature positive) and those without (ACR skin feature negative) at diagnosis. The relative frequency of skin involvement was described by the paediatric adaptation of the 2004 British Isles Lupus Assessment Group (pBILAG-2004) index. RESULTS One hundred and seventy-nine patients (74%) had ACR-defined skin involvement with no significant demographic differences compared with those without. ACR skin feature negative patients showed greater haematological (84% vs 67%), renal (43% vs 26%) (P < 0.05) and neurological (16% vs 4%) involvement (P = 0.001). Forty-two per cent of ACR skin feature negative patients had skin involvement using pBILAG-2004, which included maculopapular rash (17%), non-scaring alopecia (15%), cutaneous vasculitis (12%) and RP (12%). ACR skin feature negative patients with moderate to severe skin involvement by pBILAG-2004 showed greater renal and haematological involvement at diagnosis and over the follow-up period (P < 0.05). Higher immunosuppressive drug use in the skin feature negative group was demonstrated. CONCLUSION Patients who fulfil the ACR criteria but without any of the mucocutaneous criteria at diagnosis have an increased risk of major organ involvement. The pBILAG-2004 index has shown that other skin lesions may go undetected using the ACR criteria alone, and these lesions show a strong correlation with disease severity and major organ involvement.

Adherence to Home Physiotherapy Treatment in Children and Young People with Joint Hypermobility: A Qualitative Report of Family Perspectives on Acceptability and Efficacy

OBJECTIVE Joint hypermobility can lead to pain and motor developmental problems in children and young people (CYP). Exercise programmes may help CYP with joint hypermobility strengthen core muscle groups. Non- adherence to home physiotherapy is common. The present study aimed to understand how families experienced an intensive multidisciplinary intervention. METHOD This was a qualitative study nested within a randomized controlled trial of a multidisciplinary treatment intervention, including physiotherapy, for children aged five to 17 years. Twenty-eight families were recruited following the intervention. Semi-structured interviews were used to examine the views and expectations of parents and CYP, and examine adherence to the exercise programme. Thematic analysis of data was used to develop findings. RESULTS Parents and CYP reported that exercise reduced the symptoms of hypermobility. Parental motivation, adapting family routines, making exercise a family activity and seeing benefit increased adherence to exercise. Non-adherence to exercise was linked to lower levels of parental supervision, not understanding the treatment, not seeing benefit and not having specific time to dedicate to doing the exercises. CONCLUSION Even when exercise is seen to benefit a childs well-being, families experience challenges in adhering to a physiotherapy programme for hypermobility. Therapists can utilize findings on what enhances adherence to help CYP effectively exercise in the home setting.

Defining Juvenile Idiopathic Arthritis Remission and Optimum Time for Disease-Modifying Anti-Rheumatic Drug Withdrawal

Juvenile idiopathic arthritis (JIA) is an autoimmune disease of childhood requiring treatment with immune modulation therapy. It runs a relapsing and remitting course, with approximately half of affected children continuing with active disease into adult life. Defining clinical remission is challenging, but necessary, as it is critical in determining when potentially toxic therapy can be stopped. We found that preliminary consensus criteria for defining JIA remission are not being used in full by a representative sample of UK pediatric rheumatologists. Extending the period of remission, whilst on synthetic diseasemodifying anti-rheumatic drug (DMARD) medication, beyond 6 months does not seem to reduce the risk of relapse once medication is stopped. However, we found that most clinicians state that they still require at least 1 year in remission before DMARD withdrawal. There is increasing evidence that subclinical biomarkers may help to assess disease activity, and therefore aid clinicians in determining remission. In this review we argue that agreement on remission criteria and optimum timing of DMARD withdrawal is crucial for consistent clinical practice, and further research in this area is needed.

Carpal-tarsal osteolysis with elbow involvement

Carpal-tarsal osteolysis is a rare condition that manifests as the progressive resorption of carpal and tarsal bones in young children. The diagnosis of this condition is often difficult and delayed as the initial clinical presentation is non-specific. Radiographic changes occur gradually, are often not seen at presentation and depend on recognising loss of bone in the ossification centres of the carpus and tarsus. MRI demonstrates morphological abnormalities in the cartilaginous, as well as the osseous components, of the developing carpal and tarsal bones and therefore may be helpful in predating the radiographic changes. Ultrasound appears to contribute little to the diagnosis and may be misleading. Exclusion of other conditions, particularly juvenile idiopathic arthritis, is important in making the diagnosis. MRI can be useful in excluding an inflammatory arthropathy, and suggesting the diagnosis of carpal-tarsal osteolysis.

Evaluation of the ACR and SLICC classification criteria in juvenile-onset systemic lupus erythematosus: a longitudinal analysis.

Objectives The Systemic Lupus International Collaborating Clinics (SLICC) group proposed revised classification criteria for systemic lupus erythematosus (SLICC-2012 criteria). This study aimed to compare these criteria with the well-established American College of Rheumatology classification criteria (ACR-1997 criteria) in a national cohort of juvenile-onset systemic lupus erythematosus (JSLE) patients and evaluate how patients’ classification criteria evolved over time. Methods Data from patients in the UK JSLE Cohort Study with a senior clinician diagnosis of probable evolving, or definite JSLE, were analyzed. Patients were assessed using both classification criteria within 1 year of diagnosis and at latest follow up (following a minimum 12-month follow-up period). Results A total of 226 patients were included. The SLICC-2012 was more sensitive than ACR-1997 at diagnosis (92.9% versus 84.1% p < 0.001) and after follow up (100% versus 92.0% p < 0.001). Most patients meeting the SLICC-2012 criteria and not the ACR-1997 met more than one additional criterion on the SLICC-2012. Conclusions The SLICC-2012 was better able to classify patients with JSLE than the ACR-1997 and did so at an earlier stage in their disease course. SLICC-2012 should be considered for classification of JSLE patients in observational studies and clinical trial eligibility.

65. Blau syndrome treated with sequential biologics

headachehascompletely resolved,MPOANCAhasreducedto44 IU/ml, CRPto20 mg/LandESRto52 mm/hr.ArepeatMRIheadwithgadolinium shows ongoing or recurrent pachymeningitis with no evidence of recent or interval parenchymal abnormalities and resolution of previously demonstrated subdural fluid collections. He remains on mycophenolate mofetil 1g twice daily and a reducing regimen of prednisolone (currently 10mgdaily).He isprofoundlyataxicandhasbeencommencedonlevetiracetamforworseningintentiontremor. Discussion:Hypertrophicpachymeningitis (HP) isanextremely raredisease caused by fibrosing inflammatory processes. It may occur as the first involvement in approximately half of patientswithANCA-associated vasculitis-related HP who frequently present with headache and/or cranial neuropathy as a common symptom, in addition to ENT involvement. Recent reports on patients with MPO ANCA positive HP indicate a relationship between HP and the limited formof granulomatosis with polyangiitis (GPA). Inapreviousstudy,82%ofMPO-ANCA-positiveHPpatients were diagnosed with GPA according to Watts’ algorithm. Both seropositivity forMPO-ANCAandonesurrogatemarker forGPA(chronicsinusitis, otitismedia,ormastoiditis for>3months)wererequired forclassification as GPA in patients with MPO-ANCA-positive HP. Several studies have reported the occurrence of ANCA in HIV-positive patients, ranging from 13%to42%,withveryfewassociatedwithclinicalsmallvesselvasculitis. It has been proposed that ANCA in these patients is secondary to a markedpolyclonalB-cell responsetoHIVinfection.Whileautoantibodies may represent false positives in the context of active HIV with polyclonal gammopathy, true systemic autoimmune disease should be considered in patients with HIV infection presenting with consistent clinical features. Thus, as we increasingly find patients with reconstituted immune systems, due to effective antiretroviral therapy, autoimmune phenomena may be more common. HIV-associated pachymeningitis has not been well described, but CNS escape the phenomenon of virologic suppression in plasma but persistent, detectable HIV RNA in CSF has been described. In this case report, the co-existence and simultaneous improvement of pachymeningitis and ANCA titre indicated that pachymeningitis was a manifestation of ANCA-associated vasculitis. If left untreated, HP frequently progresses, and although it is initially steroidresponsive, clinical manifestations frequently flare up after a reduction in the dose of steroids, necessitating the addition of immunosuppressive agents. Key Learning Points: Headache and cranial neuropathies are the most common clinical presentation of hypertrophic pachymeningitis. Our patient has a diagnosis of limited GPA with a positive MPO ANCA, as he hadahistoryofotitismediaprecedinghispresentation(Watts’algorithm). TrueANCA-associatedvasculitis is rare inHIVbutdoesoccurandshould beconsideredif theclinical findingssupport it. Disclosure:P.Agrawal:None.S.Melath:None.H.Penn:None.

The efficacy and cost effectiveness of a multidisciplinary intervention strategy for the treatment of benign joint hypermobility syndrome (BJHS) in childhood. a randomised, single centre parallel group trial. (The bendy study)

Joint hypermobility is common in childhood and can be associated with musculoskeletal pain and dysfunction. Current management is delivered by a multidisciplinary team but evidence of efficacy is limited.