Long-term efficacy and safety of subcutaneous tocilizumab in clinical trials of polyarticular or systemic juvenile idiopathic arthritis.

OBJECTIVE: To investigate the safety and efficacy of subcutaneous tocilizumab (SC-TCZ) treatment in a long-term extension (LTE) of clinical trials in polyarticular or systemic juvenile idiopathic arthritis (pJIA, sJIA). METHODS: Patients with pJIA or sJIA from two open-label, 52-week phase 1 b core trials of SC-TCZ who had adequate response per investigator assessment entered the LTE and continued SC-TCZ treatment according to body weight-based dosing regimens until commercial availability or up to 5 years. Pharmacokinetics, pharmacodynamics, and efficacy were assessed for up to 3 years and safety for up to 5 years in the LTE. RESULTS: Forty-four patients with pJIA and 38 patients with sJIA entered the LTE. Tocilizumab trough concentrations were maintained within the range expected to provide clinical benefit (mean values: pJIA, ∼10 µg/ml; sJIA, ∼75 µg/ml over 3 years). Pharmacodynamic parameters (interleukin-6, soluble interleukin-6 receptor, erythrocyte sedimentation rate, C-reactive protein) were maintained throughout the LTE at levels achieved in the core trials. Inactive disease per American College of Rheumatology provisional criteria was reported for 90% (17/19) and 53% (8/15) of patients with pJIA and 91% (10/11) and 92% (12/13) of patients with sJIA in the <30 kg and ≥30 kg body weight groups, respectively. Serious adverse events in the LTE were reported in six patients with pJIA (13.6%; five serious infections) and five patients with sJIA (13.2%; one serious infection). CONCLUSION: Patients with pJIA or sJIA experienced long-term disease control with SC-TCZ treatment. Long-term safety was consistent with the known tocilizumab safety profile.

Overlap of International League of Associations for Rheumatology and Preliminary Pediatric Rheumatology International Trials Organization Classification Criteria for Nonsystemic Juvenile Idiopathic Arthritis in an Established UK Multicentre Inception Cohort.

OBJECTIVE: The goal was to assess the degree of overlap between existing International League of Associations for Rheumatology (ILAR) and preliminary Paediatric Rheumatology International Trials Organisation (PRINTO) classification criteria for juvenile idiopathic arthritis (JIA). METHODS: Participants from the Childhood Arthritis Prospective Study, a multicenter UK JIA inception cohort, were classified using the PRINTO and ILAR classification criteria into distinct categories. Systemic JIA was excluded because several classification items were not collected in this cohort. Adaptations to PRINTO criteria were required to apply to a UK health care setting, including limiting the number of blood biomarker tests required. The overlap between categories under the two systems was determined, and any differences in characteristics between groups were described. RESULTS: A total of 1,223 children and young people with a physician's diagnosis of JIA were included. Using PRINTO criteria, the majority of the patients had "other JIA" (69.5%). There was a high degree of overlap (91%) between the PRINTO enthesitis/spondylitis- and ILAR enthesitis-related JIA categories. The PRINTO rheumatoid factor (RF)-positive category was composed of 48% ILAR RF-positive polyarthritis and 52% undifferentiated JIA. The early-onset antinuclear antibodies-positive PRINTO category was largely composed of ILAR oligoarthritis (50%), RF-negative polyarthritis (24%), and undifferentiated JIA (23%). A few patients were unclassified under PRINTO (n = 3) and would previously have been classified as enthesitis-related JIA (n = 1) and undifferentiated JIA (n = 2) under ILAR. CONCLUSION: Under the preliminary PRINTO classification criteria for childhood arthritis, most children are not yet classified into a named category. These data can help support further delineation of the PRINTO criteria to ensure homogenous groups of children can be identified.

Quality improvement in juvenile idiopathic arthritis: a mixed-methods implementation pilot of the CAPTURE-JIA dataset.

BACKGROUND: A significant proportion of children and young people with juvenile idiopathic arthritis (JIA) do not achieve inactive disease during the first two years following diagnosis. Refinements to clinical care pathways have the potential to improve clinical outcomes but a lack of consistent and contemporaneous clinical data presently precludes standard setting and implementation of meaningful quality improvement programmes. This study was the first to pilot clinical data collection and analysis using the CAPTURE-JIA dataset, and to explore patient and clinician-reported feasibility and acceptability data. METHODS: A multiphase mixed-methods approach enabled prospective collection of quantitative data to examine the feasibility and efficacy of dataset collection and of qualitative data informing the context and processes of implementation. An initial paper pilot informed the design of a bespoke electronic data collection system (the Agileware system), with a subsequent electronic pilot informing the final CAPTURE-JIA data collection tool. RESULTS: Paper collection of patient data was feasible but time-consuming in the clinical setting. Phase 1 paper pilot data (121 patients) identified three themes: problematic data items (14/62 data items received >40% missing data), formatting of data collection forms and a clinician-highlighted need for digital data collection, informing Phase 2 electronic data collection tool development. Patients and families were universally supportive of the collection and analysis of anonymised patient data to inform clinical care. No apparent preference for paper / electronic data collection was reported by families. Phase 3 electronic pilot data (38 patients) appeared complete and the system reported to be easy to use. Analysis of the study dataset and a dummy longitudinal dataset confirmed that all eleven JIA national audit questions can be answered using the electronic system. CONCLUSIONS: Multicentre CAPTURE-JIA data collection is feasible and acceptable, with a bespoke data collection system highlighted as the most satisfactory solution. The study is informing ongoing work towards a streamlined and flexible national paediatric data collection system to drive quality improvement in clinical care.

A "cat"-astrophic case of Bartonella infective endocarditis causing secondary cryoglobulinemia: a case report.

BACKGROUND: Culture-negative infective endocarditis (IE) constitutes approximately 10% of all cases of IE. Bartonella endocarditis is a common cause of culture-negative endocarditis and is associated with a high mortality rate. To date, no cases of Bartonella IE has been reported in association with cryoglobulinemia in the UK. We present a unique case of Bartonella IE causing secondary cryoglobulinemia in a young female. CASE PRESENTATION: A 17-year-old female with a background of pulmonary atresia and ventricular septal defect repaired with a cardiac conduit at the age of 4, presented with a one-year history of weight loss (from 53 to 39 kg) and poor appetite. She subsequently developed a vasculitic rash and haematoproteinuria with decline in renal function, requiring urgent hospital admission. Initial blood tests showed a near normal creatinine, but a raised cystatin C. Renal biopsy showed focal necrotizing glomerulonephritis with no acute tubular necrosis or chronic change. Subsequent blood tests supported a diagnosis of cryoglobulinaemic vasculitis (high rheumatoid factor, low complement, polyclonal gammopathy, Type 3 cryoglobulin). A weak positive PR3 meant there was some uncertainty about whether this could be a primary ANCA-associated vasculitis (AAV). Initial workup for an infectious cause, including multiple blood cultures, were negative. However, an echocardiogram showed definite vegetations on her surgical conduit. The patient did not respond to empirical antimicrobials and so was referred for surgical revision of her conduit. Tissue samples obtained intra-operatively demonstrated Bartonella species. With targeted antimicrobials post-operatively, she improved with resolution of immunologic abnormalities and at last review had a normal renal profile. On reviewing her social history, she had adopted several stray cats in the preceding year; and thus, the cause of the Bartonella infection was identified. CONCLUSION: This is the first reported case of Bartonella endocarditis causing secondary cryoglobulinemia reported in the UK. The key learning points from this case include that Bartonella endocarditis can present as a cryoglobulinaemic vasculitis and should be considered in any differential when the cause of cryoglobulinaemia is not clear and to enquire about relevant exposures especially when culture-negative endocarditis is suspected.

Evaluation of Serious Infection in Pediatric Patients with Low Immunoglobulin Levels Receiving Rituximab for Granulomatosis with Polyangiitis or Microscopic Polyangiitis.

INTRODUCTION: The aim of this work was to assess the impact of prolonged low immunoglobulin (IgG or IgM) serum concentrations on the potential cumulative serious infection (SI) risk in pediatric patients following rituximab treatment for granulomatosis with polyangiitis or microscopic polyangiitis (GPA/MPA) in PePRS. METHODS: Patients aged ≥ 2 to < 18 years received four weekly intravenous rituximab infusions of 375 mg/m2 and concomitant glucocorticoid taper. After 6 months, patients could receive further rituximab and/or other immunosuppressants per investigator discretion. Immunoglobulin levels and SIs were assessed throughout the 4.5-year observation period. Prolonged low IgG or IgM was defined as below the lower limit of normal age-specific reference range for ≥ 4 months. RESULTS: A total of 25 patients were included, of whom 19 (76%) had GPA and six (24%) had MPA; 18 (72%) had newly diagnosed disease and seven (28%) had relapsing disease. All 25 patients completed the rituximab induction regimen; 24 completed ≥ 18 months of follow-up. At month 18, eighteen patients (72%) had prolonged low IgG; 19 (76%), prolonged low IgM; and 15 (60%), both. Seven patients (28%) had nine SIs; one occurred during or after prolonged low IgG only, two during or after prolonged low IgM only, and six during or after concurrent prolonged low IgG and IgM. No patients died or discontinued the study due to SI. All patients had complete and sustained peripheral B-cell depletion for ≥ 6 months. CONCLUSIONS: The majority of pediatric patients who received rituximab for GPA/MPA with prolonged low immunoglobulin levels did not experience SIs. In patients with SIs, these events were manageable, and the number of SIs did not increase over time or with multiple rituximab treatments. These observations are consistent with the rituximab safety profile in adults with GPA/MPA. TRIAL REGISTRATION: ClinicalTrials.gov identifier, NCT01750697.

Phase IIa Global Study Evaluating Rituximab for the Treatment of Pediatric Patients With Granulomatosis With Polyangiitis or Microscopic Polyangiitis.

OBJECTIVE: To assess the safety, tolerability, pharmacokinetics, and efficacy of rituximab (RTX) in pediatric patients with granulomatosis with polyangiitis (GPA) or microscopic polyangiitis (MPA). METHODS: The Pediatric Polyangiitis Rituximab Study was a phase IIa, international, open-label, single-arm study. During the initial 6-month remission-induction phase, patients received intravenous infusions of RTX (375 mg/m2 body surface area) and glucocorticoids once per week for 4 weeks. During the follow-up period, patients could receive further treatment, including RTX, for GPA or MPA. The safety, pharmacokinetics, pharmacodynamics, and exploratory efficacy outcomes with RTX were evaluated. RESULTS: Twenty-five pediatric patients with new-onset or relapsing disease were enrolled at 11 centers (19 with GPA [76%] and 6 with MPA [24%]). The median age was 14 years (range 6-17 years). All patients completed the remission-induction phase. During the overall study period (≤4.5 years), patients received between 4 and 28 infusions of RTX. All patients experienced ≥1 adverse event (AE), mostly grade 1 or grade 2 primarily infusion-related reactions. Seven patients experienced 10 serious AEs, and 17 patients experienced 31 infection-related AEs. No deaths were reported. RTX clearance correlated with body surface area. The body surface area-adjusted RTX dosing regimen resulted in similar exposure in both pediatric and adult patients with GPA or MPA. Remission, according to the Pediatric Vasculitis Activity Score, was achieved in 56%, 92%, and 100% of patients by months 6, 12, and 18, respectively. CONCLUSION: In pediatric patients with GPA or MPA, RTX is well tolerated and effective, with an overall safety profile comparable to that observed in adult patients with GPA or MPA who receive treatment with RTX. RTX is associated with a positive risk/benefit profile in pediatric patients with active GPA or MPA.

Telemedicine: improving clinical care and medical education in paediatrics.

The COVID-19 pandemic has led to a rapid increase in the use of telemedicine. This is likely to continue when the social distancing restrictions have been eased. There have been a number of technological advances that have contributed to the roll-out and improved quality of telemedicine consultations. Telemedicine has a number of benefits including facilitating home working for clinicians, reduce travel time for families and allows multidisciplinary team working across different sites. In addition to these clinical benefits there are also the environmental benefits of reduced travel to and from the hospital setting. There are limitations to this change in practice including the need for repeat appointments if a telemedicine facilitated contact is not adequate and the perpetuation of inequality for vulnerable families, the so called "digital divide". Due to the increase in the use of telemedicine it is important that clinicians develop effective consultation practices including appropriate selection of patients, technical setup and consultation tools. In order to ensure trainees are developing appropriate skills in telemedicine, educational opportunities should be developed including structured assessment tools to allow the demonstration of competence in this area.

Mycophenolate Mofetil Versus Cyclophosphamide for Remission Induction in Childhood Polyarteritis Nodosa: An Open-Label, Randomized, Bayesian Noninferiority Trial.

OBJECTIVE: Cyclophosphamide (CYC) is used in clinical practice off-label for the induction of remission in childhood polyarteritis nodosa (PAN). Mycophenolate mofetil (MMF) might offer a less toxic alternative. This study was undertaken to explore the relative effectiveness of CYC and MMF treatment in a randomized controlled trial (RCT). METHODS: This was an international, open-label, Bayesian RCT to investigate the relative effectiveness of CYC and MMF for remission induction in childhood PAN. Eleven patients with newly diagnosed childhood PAN were randomized (1:1) to receive MMF or intravenous CYC; all patients received the same glucocorticoid regimen. The primary end point was remission within 6 months while compliant with glucocorticoid taper. Bayesian distributions for remission rates were established a priori for MMF and CYC by experienced clinicians and updated to posterior distributions on trial completion. RESULTS: Baseline disease activity and features were similar between the 2 treatment groups. The primary end point was met in 4 of 6 patients (67%) in the MMF group and 4 of 5 patients (80%) in the CYC group. Time to remission was shorter in the MMF group compared to the CYC group (median 7.1 weeks versus 17.6 weeks). No relapses occurred in either group within 18 months. Two serious infections were found to be likely linked to MMF treatment. Physical and psychosocial quality-of-life scores were superior in the MMF group compared to the CYC group at 6 months and 18 months. Combining the prior expert opinion with results from the present study provided posterior estimates of remission of 71% for MMF (90% credibility interval [90% CrI] 51, 83) and 75% for CYC (90% CrI 57, 86). CONCLUSION: The present results, taken together with prior opinion, indicate that rates of remission induction in childhood PAN are similar with MMF treatment and CYC treatment, and MMF treatment might be associated with better health-related quality of life than CYC treatment.

Validation of novel patient-centred juvenile idiopathic arthritis-specific patient-reported outcome and experience measures (PROMs/PREMs).

BACKGROUND: Measuring the outcomes that matter to children and young people (CYP) with juvenile idiopathic arthritis (JIA), is a necessary precursor to patient-centred improvements in quality of clinical care. We present a two-centre validation of novel JIA patient-reported outcome and experience measures (PROM and PREM) developed as part of the CAPTURE-JIA project. METHODS: CYP with JIA were recruited from paediatric rheumatology clinics, completing the CAPTURE-JIA PROM and PREM, CHAQ and CHU 9D. A subset participated in face-to-face interviews and completed the PROM/PREM 1 week later. The OMERACT filter was applied and the three domains of validation assessed. Truth assessments included cognitive interviewing, sensitivity analysis and Spearman's correlations. Discrimination assessments included specificity and reliability testing. Feasibility was assessed using time to form completion and proportion of missing data. RESULTS: Eighty-two CYP and their families were recruited; ten cognitive interviews and fifteen PROM/PREM test/retests were conducted. Truth: CYP and parents understood the PROM/PREM and felt important areas were covered. PROM criteria had high sensitivities (> 70%) against similar items on the CHU 9D, with the exception of fatigue (58%). Correlations between similar PROM and CHU 9D criteria were moderate to very strong (coefficients 0.40-0.82.) Discrimination: high specificities (> 70%) on corresponding PROM and CHU 9D domains. Feasibility: median completion times for PROM 60 s (IQR 38-75) and PREM 49 s (IQR 30-60) respectively. CONCLUSION: The CAPTURE-JIA PROM and PREM are valid and feasible in UK paediatric rheumatology clinics. Embedding routine collection into clinical care would be a major step towards improving quality of care.

Impact of COVID-19 on training: a single-centre survey of trainees.

To review the impact of COVID-19 on postgraduate paediatric training, a 10-question online survey was designed to evaluate trainees' training opportunities. 56 trainees working at a single centre, Alder Hey Children's Hospital, completed the survey. The majority of trainees felt that COVID-19 had affected their training. Trainees wanted to become involved in Quality Improvement Programs. Face-to-face teaching was still favourable but web-based teaching methods were preferred. Novel online, Worked Based Assessment clinics were well received. COVID-19 has affected traditional learning opportunities but offered a new positive range of digital solutions to give and store educational material.

CAPTURE-JIA: a consensus-derived core dataset to improve clinical care for children and young people with juvenile idiopathic arthritis.

OBJECTIVES: Data collected during routine clinic visits are key to driving successful quality improvement in clinical services and enabling integration of research into routine care. The purpose of this study was to develop a standardized core dataset for juvenile idiopathic arthritis (JIA) (termed CAPTURE-JIA), enabling routine clinical collection of research-quality patient data useful to all relevant stakeholder groups (clinicians, service-providers, researchers, health service planners and patients/families) and including outcomes of relevance to patients/families. METHODS: Collaborative consensus-based approaches (including Delphi and World Café methodologies) were employed. The study was divided into discrete phases, including collaborative working with other groups developing relevant core datasets and a two-stage Delphi process, with the aim of rationalizing the initially long data item list to a clinically feasible size. RESULTS: The initial stage of the process identified collection of 297 discrete data items by one or more of fifteen NHS paediatric rheumatology centres. Following the two-stage Delphi process, culminating in a consensus workshop (May 2015), the final approved CAPTURE-JIA dataset consists of 62 discrete and defined clinical data items including novel JIA-specific patient-reported outcome and experience measures. CONCLUSIONS: CAPTURE-JIA is the first 'JIA core dataset' to include data items considered essential by key stakeholder groups engaged with leading and improving the clinical care of children and young people with JIA. Collecting essential patient information in a standard way is a major step towards improving the quality and consistency of clinical services, facilitating collaborative and effective working, benchmarking clinical services against quality indicators and aligning treatment strategies and clinical research opportunities.

Short-term outcome of surgical arthrodiastasis of the ankle with Ilizarov frame in a cohort of children and young people with juvenile idiopathic arthritis.

OBJECTIVES: Despite medical advances, life-changing articular damage may still occur in patients with JIA. We report a cohort with destructive arthropathy of the ankle treated by surgical arthrodiastasis. METHODS: Eight patients (nine ankles) received arthrodiastasis by means of an Ilizarov frame between 2009 and 2013. Patient- and clinician-reported outcome measures were collated prospectively, with retrospective analysis of demographics, disease and pre-surgical treatment. RESULTS: Pre-surgery, all patients received IA CS (mean 0.8 injections/year) and MTX (mean diagnosis to treatment 3.8 years; two of eight started within 3 months). Seven of eight patients received biologic drugs. Pain scores improved by 56 and 29% (P < 0.005) at 6 and 12 months post-frame removal. American Academy Orthopaedic Foot and Ankle Society ankle-hindfoot scale, Oxford Ankle Foot Questionnaire-Child and Oxford Ankle Foot Questionnaire-Parent scores improved by 171, 62 and 80%, respectively (P < 0.005) at 12 months post-frame removal. Patients remained satisfied with surgical treatment for a mean of 13.3 months. There was transient pin site infection in three patients, and all patients had radiological improvement in joint space. CONCLUSION: Arthrodiastasis with an Ilizarov frame is a safe, well-tolerated technique that should be considered as a short-term joint-preserving procedure to improve pain and function when damage has occurred. Delays to systemic medical treatment in this cohort would be considered out-with standard modern practice but, although less prevalent, destructive ankle arthropathy continues to occur in JIA, and we believe this study to be relevant. The ankle is particularly susceptible to damage and, even if localized, should be treated early and aggressively with DMARDs and rapid progression to biologic therapies. LEVELOF EVIDENCE: Level IV.

Development of a national audit tool for juvenile idiopathic arthritis: a BSPAR project funded by the Health Care Quality Improvement Partnership.

Objective: Timely access to holistic multidisciplinary care is the core principle underpinning management of juvenile idiopathic arthritis (JIA). Data collected in national clinical audit programmes fundamentally aim to improve health outcomes of disease, ensuring clinical care is equitable, safe and patient-centred. The aim of this study was to develop a tool for national audit of JIA in the UK. Methods: A staged and consultative methodology was used across a broad group of relevant stakeholders to develop a national audit tool, with reference to pre-existing standards of care for JIA. The tool comprises key service delivery quality measures assessed against two aspects of impact, namely disease-related outcome measures and patient/carer reported outcome and experience measures. Results: Eleven service-related quality measures were identified, including those that map to current standards for commissioning of JIA clinical services in the UK. The three-variable Juvenile Arthritis Disease Activity Score and presence/absence of sacro-iliitis in patients with enthesitis-related arthritis were identified as the primary disease-related outcome measures, with presence/absence of uveitis a secondary outcome. Novel patient/carer reported outcomes and patient/carer reported experience measures were developed and face validity confirmed by relevant patient/carer groups. Conclusion: A tool for national audit of JIA has been developed with the aim of benchmarking current clinical practice and setting future standards and targets for improvement. Staged implementation of this national audit tool should facilitate investigation of variability in levels of care and drive quality improvement. This will require engagement from patients and carers, clinical teams and commissioners of JIA services.

Hypercalcaemic Pancreatitis, Adrenal Insufficiency, Autoimmune Thyroiditis and Diabetes Mellitus in a girl with Probable Sarcoidosis.

INTRODUCTION: Sarcoidosis is a multisystemic granulomatous disease with diverse and often non-specific symptoms during childhood. The clinical manifestations sometimes include endocrinopathies related to sarcoid infiltration of various endocrine organs, but more commonly due to the associated autoimmune endocrine disorders. There are only a few reports of multiple autoimmune and non-autoimmune endocrine problems occurring simultaneously in patients with sarcoidosis. We report a girl with probable sarcoidosis who also had Hashimoto's thyroiditis, Type 1 diabetes (T1D) and secondary adrenal insufficiency. CASE PRESENTATION: A 9-year-old girl previously diagnosed with autoimmune hypothyroidism and vitamin D deficiency, presented with hypercalcemic pancreatitis after initiating vitamin D supplementation that lead to a diagnosis of probable sarcoidosis. Secondary adrenal insufficiency and T1D were subsequently diagnosed. Her angiotensin converting enzyme levels on 2 occasions were 106 and 135 nmol/mL/min (normal range 10 - 43). All investigations conducted to exclude several infectious and malignant conditions that may mimic sarcoidosis were negative. The patient showed a good response to treatment with hydrocortisone, levothyroxine, insulin and methotrexate. CONCLUSIONS: To our knowledge, ours is the youngest ever patient reported in the literature with sarcoidosis to develop multiple autoimmune and non-autoimmune endocrinopathies.

Effect of socioeconomic conditions on frequent complaints of pain in children: findings from the UK Millennium Cohort Study.

BACKGROUND: Frequent complaints of pain (FCP) are common in high-income countries, affecting about 25% of children, and may have significant adverse consequences including prolonged school absence and disability. Most FCP are unexplained, and the aetiology is poorly understood. This study aimed to identify risk factors for FCP and explore how risk factors explain variation in pain reporting by childhood socioeconomic conditions (SECs). METHODS: Analysis of the UK Millennium Cohort Study, including 8463 singleton children whose parents provided data throughout the study. At 11 years, mothers were asked whether their child frequently complains of pain. Risk ratios (RR) and 95% CIs for FCP were estimated using Poisson regression, according to maternal education. Other risk factors were explored to assess if they attenuated any association between FCP and SECs. RESULTS: 32.3% of children frequently complained of pain. Children of mothers with no educational qualifications were more likely to have FCP than children of mothers with higher degrees (RR 2.06, 95% CI 1.64 to 2.59) and there was a clear gradient across the socioeconomic spectrum. Female sex, fruit consumption, childhood mental health and maternal health measures were associated with childhood FCP in univariable and multivariable analyses. Inclusion of these factors within the model attenuated the RR by 17% to 1.70 (95% CI 1.36 to 2.13). CONCLUSION: In this representative UK cohort, there was a significant excess of FCP reported in less advantaged children that was partially attenuated when accounting for indicators of parental and childhood mental health. Addressing these factors may partially reduce inequalities in childhood FCP.

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.