Enrolment of the first paediatric cohort into the Australian lupus registry and biobank: A single-centre experience.

INTRODUCTION: We aim to report on the feasibility of establishment of the first paediatric cohort as part of the longitudinal database of the Australian Lupus Registry and Biobank (ALRB) and to describe the enrolment data with a focus on clinical characteristics, serological data, treatment strategies and patient/parent-reported outcome measures. METHODS: All patients under the age of 18 years with a diagnosis of systemic lupus erythematosus (SLE) attending the paediatric rheumatology service of a single, tertiary hospital were identified. Patients were enrolled in the ALRB if they met ≥4/11 of the American College of Rheumatology (ACR) 1997 SLE classification criteria or the Systemic Lupus International Collaborating Clinics (SLICC) 2012 classification criteria. Enrolment data including demographics, clinical characteristics, serological profiles, disease activity and damage assessments were recorded. Peds-QL Rheumatology and General Modules were used to assess patient and parent-reported outcomes. RESULTS: Twenty-seven patients were eligible for inclusion, with 26 patients (96%) consenting for enrolment. Twenty-five patients (92%) consented for biobanking. Twenty patients (77%) were female. The median age at enrolment was 16 years (interquartile range (IQR) 13.7, 17.4). The median disease duration from diagnosis was 3.2 years (IQR 1.4, 5.3). Sixteen patients (62%) had synovitis, 16 (62%) had cutaneous involvement, 4 (15%) had serositis, 17 (65%) had haematological involvement and 7 (27%) had renal involvement at enrolment. Nineteen patients (73%) were prescribed at least two disease-modifying anti-rheumatic medications (DMARDs). Hydroxychloroquine (n = 22, 85%) and mycophenolate mofetil (n = 9, 35%) were the most commonly prescribed DMARDs. The median SLEDAI-2K score was 2 (IQR 2, 4). Six patients (23%) had active disease (SLEDAI-2K ≥6) at enrolment. Three patients (11.5%) had reported damage using the SLICC/ACR Damage Index. Twenty-three children (88%) and eighteen parents (69%) completed the Paediatric Quality of Life Inventory. Quality of life scores reported across domains of physical, emotional, social and school functioning at enrolment were comparable to previously studied paediatric cohorts with SLE and other chronic diseases. CONCLUSION: We have established our centre as the first paediatric participating site of the ALRB, providing contemporary data on the clinical characteristics, serological profile and health-related quality of life outcomes of Australian children with SLE. Paediatric involvement with this national registry will provide a unique perspective for future clinical and scientific research. Collection of Australian-specific paediatric longitudinal data will also enable a broader understanding of SLE within a multicultural Australian population.

The transition process for paediatric rheumatology clinic patients at a single tertiary paediatric rheumatology centre in Australia.

AIM: This study aimed to examine the transition process of paediatric rheumatology patients from the Monash Children's Hospital (MCH) in Melbourne in order to identify areas that could be improved. METHODS: Retrospective review of clinical data from the rheumatology database of paediatric rheumatology patients eligible for transition between January 2015 and September 2020. RESULTS: One hundred and sixty-five patients were included; 57 patients were transitioned. Of patients transitioned to an adult service, 38 (88%) were on medication and 14 (33%) had active disease. All patients transitioned to the general practitioner (GP) had inactive disease off medication. Juvenile idiopathic arthritis (JIA) (non-systemic) was the most common diagnosis in patients transitioned. The mean age at which transition was first discussed was 18.0 years; the first referral was made at a mean of 18.3 years. The mean age at the first adult appointment was 18.5 years. Thirty-nine (91%) patients had a referral completed and 8 (19%) had a transfer letter. Thirteen (93%) patients transferred to the GP had a transfer letter. Transfer documents to an adult public rheumatology service rated 4.3 for quality, compared to 5.5 to the GP. Transfer of care was confirmed in 40 (93%) patients transitioned to an adult service; however, correspondence was available for only 3 (7%). CONCLUSION: Although the transition process at MCH was adequate, it could be improved through earlier discussion of the process and improved referrals and documentation. A readiness-to-transfer checklist and a young adult clinic have the potential to improve the process of transition to adult rheumatology care.

Patterns and rates of confirmed transfer of care of patients with juvenile idiopathic arthritis at a tertiary paediatric rheumatology centre.

BACKGROUND: Disease activity in juvenile idiopathic arthritis (JIA) commonly persists into adulthood. Transfer of JIA patients to adult healthcare services can be challenging, with prior studies showing poor rates of success. AIMS: This audit sought to examine characteristics of patients undergoing transfer of care within the rheumatology unit at the Royal Children's Hospital in Melbourne, with the aim of identifying areas for improvement. Specifically, we sought to determine the rate at which confirmation of established care with an adult service (confirmed transfer of care) was documented in the patient chart. METHODS: Patients with a diagnosis of JIA who turned 18 years of age between 2012 and 2019 were identified. A chart review was undertaken to collect relevant data. RESULTS: One hundred and seventy-seven patients were identified. In all, 64% (114/177) were referred for adult care. The commonest JIA subtypes referred were seronegative polyarticular (35/114; 30.7%) and oligoarticular JIA (22/114; 19.3%). Documentation of confirmed transfer of care occurred in 62.3% (71/114), with correspondence received from adult services in 49.1% (56/114). There was no difference in rate of return correspondence from public versus private providers (45% vs 53.8%; P = 0.38). The use of 'backstop appointments' was more likely in those with confirmed transfer of care (66% vs 30%; P = 0.0002). CONCLUSIONS: Lack of confirmed transfer of care for JIA patients is common and carries a risk of suboptimal outcomes. Strategies to improve communication with adult services, the routine use of 'backstop' appointments and vigilance regarding potential loss to follow up at the time of transfer would minimise this risk.

Paediatric acute non-traumatic limp presenting to the emergency department: a retrospective observational study.

BACKGROUND: Acute non-traumatic limp in children has many causes, ranging from common benign and self-limiting disease to serious time-sensitive emergencies such as septic arthritis. We aimed to (1) describe the epidemiology and workup of paediatric acute non-traumatic limp presentation in three Australian EDs and (2) compare investigations and treatment between a tertiary paediatric centre and two non-tertiary centres. METHODS: A retrospective chart review of children aged 0-16 years, with an initial presentation of non-traumatic limp to three EDs in Melbourne, Australia. Data on presentation, management and outcomes was systematically collected on all eligible patients. RESULTS: Of 63 941 presentations over a 12-month period, 475 (0.7%) met inclusion criteria. The median (IQR) age of presentation was 5 (3-8) years, with a male predominance (61%). Blood tests and imaging were performed in 39% and 51%, respectively. 34% of presentations had no investigations. The most frequent ED diagnoses were transient synovitis (37%) and viral myositis (16%). 84% were discharged home after ED evaluation. Compared with the two non-tertiary hospitals, children who presented to the tertiary centre were less likely to have any investigation performed (OR=0.41, 95% CI: 0.27 to 0.62, p<0.001) and more likely to be discharged home after evaluation (OR=4.67, 95% CI: 2.79 to 7.81, p<0.001). CONCLUSION: Although mostly due to benign disorders, an important number of limping children who presented to the ED had serious disease, with approximately one-third of these not diagnosed at the initial ED visit. There is large variation in workup including blood test, imaging and decisions regarding ED disposition.

Three- and five-year outcomes of an inception cohort of Australian children with juvenile idiopathic arthritis.

BACKGROUND: To describe the 3- and 5-year outcomes of an inception cohort of Australian children with JIA for whom 1-year outcomes have previously been published. METHODS: Data regarding clinical outcomes of the original cohort of 134 patients at 3 and 5 years were sought. Relevant clinical features and medication exposures entered prospectively into an electronic record were collected and analyzed using descriptive statistics. RESULTS: Data were available for 110 and 98 patients at 3 and 5 years, respectively. The proportion of patients with active joints progressively decreased from 34% at 12 months to 21% at 3 years and 16% at 5 years. Cumulative exposure to methotrexate increased between 3 and 5 years (75%-80%), however, point prevalence use decreased (45%-41%). Cumulative exposure and point prevalence use of bDMARDS both increased between 3 and 5 years; 30%-42% and 29%-33%, respectively. Thirty-five percent of patients had inactive joint disease off medications at 5 years, which occurred most frequently in patients with sJIA and oligoarthritis. CONCLUSION: Five-year outcomes of Australian children with JIA are good, with only a small minority having ongoing active joint disease at 5 years. bDMARDS play an increasing role in management over time; however, methotrexate use remains significant. A majority of children remain on medications at 5 years.

Test characteristics of history, examination and investigations in the evaluation for septic arthritis in the child presenting with acute non-traumatic limp. A systematic review.

BACKGROUND: Septic arthritis is an uncommon but potentially significant diagnosis to be considered when a child presents to the emergency department (ED) with non-traumatic limp. Our objective was to determine the diagnostic accuracy of clinical findings (history and examination) and investigation results (pathology tests and imaging) for the diagnosis of septic arthritis among children presenting with acute non-traumatic limp to the ED. METHODS: Systematic review of the literature published between 1966 and June 2019 on MEDLINE and EMBASE databases. Studies were included if they evaluated children presenting with lower limb complaints and evaluated diagnostic performance of items from history, physical examination, laboratory testing or radiological examination. Data were independently extracted by two authors, and quality assessment was performed using the Quality Assessment Tool for Diagnostic Accuracy Studies 2 tool. RESULTS: 18 studies were identified, and included 2672 children (560 with a final diagnosis of septic arthritis). There was substantial heterogeneity in inclusion criteria, study setting, definitions of specific variables and the gold standard used to confirm septic arthritis. Clinical and investigation findings were reported using varying definitions and cut-offs, and applied to differing study populations. Spectrum bias and poor-to-moderate study design quality limit their applicability to the ED setting.Single studies suggest that the presence of joint tenderness (n=189; positive likelihood ratio 11.4 (95% CI 5.9 to 22.0); negative likelihood ratio 0.2 (95% CI 0.0 to 1.2)) and joint effusion on ultrasound (n=127; positive likelihood ratio 8.4 (95% CI 4.1 to 17.1); negative likelihood ratio 0.2 (95% CI 0.1 to 0.3)) appear to be useful. Two promising clinical risk prediction tools were identified, however, their performance was notably lower when tested in external validation studies. DISCUSSION: Differentiating children with septic arthritis from non-emergent disorders of non-traumatic limp remains a key diagnostic challenge for emergency physicians. There is a need for prospectively derived and validated ED-based clinical risk prediction tools.

Vaccinations Do Not Increase Arthritis Flares in Juvenile Idiopathic Arthritis: A Study of the Relationship between Routine Childhood Vaccinations on the Australian Immunisation Schedule and Arthritis Activity in Children with Juvenile Idiopathic Arthritis.

BACKGROUND: Juvenile idiopathic arthritis (JIA) is a collective term for a group of inflammatory conditions of uncertain origin, which causes chronic arthritis in one or more joints. The clinical course of JIA is characterised by episodes of increased activity, termed flares. Vaccinations have previously been proposed as a "trigger" for some flares, although evidence supporting this is scant. OBJECTIVE: To explore whether routine childhood vaccinations are associated with an increased risk of flares of arthritis activity in children with JIA. METHODS: Patients aged below 6 years with a diagnosis of JIA were recruited from the Rheumatology Clinical Database at the Royal Children's Hospital, Melbourne, Australia, from 1 January 2010 to 30 April 2016. Patient immunisation status was cross-checked with the Australian Childhood Immunisation Register (ACIR). The self-controlled case series methodology (Rowhani-Rahbar et al., 2012) was applied to determine whether the risk of arthritis flares in the three months following immunisation was greater than the baseline risk for each patient. RESULTS: 138 patients were included in the study. 32 arthritis flares occurred in the 90 days following immunisation. The risk of arthritis flares during the 90 days following immunisation was reduced compared with patients' baseline risk (RR 0.59 (95% CI 0.39-0.89, p = 0.012)). CONCLUSION: Routine childhood immunisations were not associated with arthritis flare onset in patients with JIA. The risk of arthritis flares in the 90 days following vaccination was lower than the baseline risk. In the context of COVID19, vaccination will not increase interaction with the healthcare system beyond the immunisation encounter.

Cognitive outcomes of childhood primary CNS vasculitis.

OBJECTIVE: To characterize the clinical cognitive phenotypes and severity of cognitive burden according to disease subtype in children with primary central nervous system vasculitis (cPACNS). METHOD: This retrospective multicenter inflammatory brain disease database study examined the neuropsychological outcomes of 80 children (44 male; mean age = 7.89 years, SD = 4.17) consecutively diagnosed with primary CNS vasculitis between 1992 and 2016. Twenty-one children had small-vessel disease (AN_cPACNS), and 59 had large-vessel disease (including 49 nonprogressive [APNP_cPACNS] and 10 progressive [APP_cPACNS]). Neuroimaging revealed MRI abnormalities in 100% and 90% of children with large- and small-vessel vasculitis, respectively. The primary outcomes were Full Scale IQ (FSIQ) and the index scores from the Wechsler Intelligence Scale for Children-III (WISC-III, WISC-IV, and WISC-V). Analyses explored the effect of disease subtype. RESULTS: Intellectual functioning was assessed on average 2.82 years after symptom onset. Children with small-vessel CNS vasculitis had significantly lower FSIQ scores than did those with large-vessel CNS vasculitis (Ms = 81.90 vs. 94.82; p = .04). Intellectual disability (FSIQ < 70) was more frequent in children with small-vessel disease (24% vs. 5%). All groups displayed lower Working Memory and Processing Speed index scores relative to Verbal Comprehension and Perceptual Reasoning index scores. Group differences in FSIQ remained significant after controlling for the presence of seizures. CONCLUSION: Children with small-vessel CNS vasculitis are more likely to demonstrate deficits in intellectual functioning than are those with large-vessel disease, and children with both types of CNS vasculitis demonstrate relatively poor working memory and processing speed. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Treatment Options for Resistant Kawasaki Disease.

"Resistant" Kawasaki disease is defined by the American Heart Association as failure to respond within 36 h following the first dose of intravenous immunoglobulin. The optimal management of resistant Kawasaki disease remains uncertain, the outcomes are potentially serious, and the cost of some treatments is considerable. We review the current evidence to guide treatment of resistant Kawasaki disease. Given the relative rarity, there are few trial data, and studies tend to be small and methodologically heterogeneous, making interpretation difficult and limiting generalisability. The literature on resistant Kawasaki disease should be interpreted with reference to current expert consensus guidelines.

Juvenile idiopathic arthritis managed in the new millennium: one year outcomes of an inception cohort of Australian children.

BACKGROUND: The advent of new treatments for Juvenile Idiopathic Arthritis (JIA) has prompted interest in systematically studying the outcomes of patients treated in the 'modern era'. Such data provide both benchmarks for assessing local outcomes and important information for use in counselling families of newly diagnosed patients. While data are available for cohorts in Europe and North America, no such data exist for Australian patients. The aim was to examine the demographics, treatment and outcomes at 12 months of an inception cohort of newly diagnosed patients with JIA at a single tertiary referral paediatric rheumatology centre in Australia. METHODS: Retrospective review of prospectively collected data from patients newly diagnosed with JIA between 2010 and 2014 at the Royal Children's Hospital in Melbourne. RESULTS: One hundred thirty four patients were included (62% female). Oligoarthritis was the single largest category of JIA (36%) and rheumatoid factor positive polyarthritis the least common (2%). Undifferentiated JIA accounted for 13% of patients and was the third largest category. Across the cohort 94% received NSAIDs, 53% oral steroids, 62% methotrexate and 15% a biologic DMARD. Intra-articular steroids were used in 62%, most commonly in the oligoarticular subtype (94%). 95% of patients achieved a joint count of zero at a median of 4.1 months, however flares occurred in 42%. At 12 months 65% had no active joint disease, though more than half remained on medication. CONCLUSION: Australian children with JIA managed in the modern era have similar characteristics and achieve short term outcomes comparable to cohorts in Europe and North America, with high rates of joint remission in the first 12 months of follow-up but with a significant relapse rate and requirement for ongoing medication.

Clinical features and disease course of patients with juvenile dermatomyositis.

OBJECTIVE: To describe the clinical features and course of a cohort of patients with juvenile dermatomyositis (JDM) at a tertiary referral pediatric centre in Australia and examine changes in diagnostic and therapeutic approach over time. METHODS: Retrospective review of patients diagnosed with JDM at the Royal Children's Hospital, Melbourne, between 1989 and 2010. RESULTS: Fifty-seven patients were identified. The female : male ratio was 2 : 1 and median age at diagnosis was 7.1 years (2.2-15.3). At diagnosis, 95% had weakness, all had typical rash and 68% had nailfold capillary changes. Calcinosis was not present in any patients at diagnosis and occurred in 18% over time. Creatine kinase, lactate dehydrogenase, aspartate aminotransferase, alanine aminotransferase and aldolase levels were abnormal in 65%, 92%, 88%, 58% and 100%, respectively. Magnetic resonance imaging (MRI) was abnormal in 97% of patients, electomyograph (EMG) in 83% and muscle biopsy in all four patients in whom it was performed. MRI was used in 86% (24/28) of patients diagnosed after 2000. Muscle biopsy was used in four and EMG in no patients over the same period. Treatment used throughout the disease course included oral steroids (93%), high-dose pulse intravenous steroids (82%), methotrexate (63%), intravenous immunoglobulin (32%) and cyclosporin (18%). The disease was monophasic in 46.7% (21/45), polyphasic in 17.7% (8/45) and chronic in 35.5% (16/45). CONCLUSIONS: Australian patients with JDM have similar characteristics to previously described cohorts. In practice, MRI has replaced the invasive diagnostic tests included in the Bohan and Peter criteria for the diagnosis of JDM. The early use of disease-modifying anti-rheumatic drugs has become the most common treatment approach.

Primary and secondary central nervous system vasculitis.

Central nervous system vasculitis is an increasingly recognized inflammatory brain disease causing devastating neurological deficits and psychiatric manifestations in previously healthy children. Primary central nervous system vasculitis represents an isolated inflammatory attack targeting the cerebral vessels. In contrast, in children with secondary central nervous system vasculitis, an underlying condition can be identified. The spectrum of childhood primary and secondary central nervous system vasculitis is rapidly expanding, as is the differential diagnosis including nonvasculitic inflammatory brain diseases and noninflammatory vasculopathies. Early recognition, rapid diagnostic evaluation, and initiation of treatment have led to improved morbidity and mortality. This review focuses on clinical, laboratory, and neuroimaging characteristics of the distinct subtypes of primary childhood central nervous system vasculitis, reports the etiology of secondary central nervous system vasculitis, provides an overview of the differential diagnosis, and reviews the current approaches in treatment.

Juvenile idiopathic arthritis.

Juvenile idiopathic arthritis (JIA) encompasses a complex group of disorders with arthritis as a common feature. This article provides the pediatrician with a review of the epidemiology, classification, clinical manifestations, and complications of JIA. It also provides an update on the current understanding of the cause of JIA and recent developments in management and a recent review of the long-term outcome in JIA.

Rotavirus cerebellitis: new aspects to an old foe?

Rotavirus infection is a significant cause of childhood morbidity and mortality worldwide. Although infection primarily causes gastroenteritis and dehydration, systemic signs and neurologic manifestations in rotavirus infection are widely recognized. The pathophysiologic origins of neurologic signs in rotavirus infection remain incompletely understood. We present a 4-year-old girl with clinical features of severe cerebellitis in association with abnormalities detected on magnetic resonance imaging. Rotavirus nucleic acid was demonstrated in both serum and cerebrospinal fluid. Severe neurologic sequelae remain after 2 years of follow-up. This report adds further evidence supporting a direct role for rotavirus in neurologic illness.