Real world treatment of juvenile-onset systemic lupus erythematosus: Data from the UK JSLE cohort study.

BACKGROUND: In the absence of clinical trials evidence, Juvenile-onset Systemic Lupus Erythematosus (JSLE) treatment plans vary. AIM: To explore 'real world' treatment utilising longitudinal UK JSLE Cohort Study data. METHODS: Data collected between 07/2009-05/2020 was used to explore the choice/sequence of immunomodulating drugs from diagnosis. Multivariate logistic regression determined how organ-domain involvement (pBILAG-2004) impacted treatment choice. RESULT: 349 patients met inclusion criteria, median follow-up 4-years (IQR:2,6). Mycophenolate mofetil (MMF) was most commonly used for the majority of organ-domains, and significantly associated with renal involvement (OR:1.99, 95% CI:1.65-2.41, pc < 0.01). Analyses assessing the sequence of immunomodulators focused on 197/349 patients (meeting relevant inclusion/exclusion criteria). 10/197 (5%) solely recieved hydroxychloroquine/prednisolone, 62/197 (31%) received a single-immunomodulator, 69/197 (36%) received two, and 36/197 patients (28%) received ≥three immunomodulators. The most common first and second line immunomodulator was MMF. Rituximab was the most common third-line immunomodulator. CONCLUSIONS: Most UK JSLE patients required ≥two immunomodulators, with MMF used most commonly.

Attainment of low disease activity and remission targets reduces the risk of severe flare and new damage in childhood lupus.

OBJECTIVES: To assess the achievability and effect of attaining low disease activity (LDA) or remission in childhood-onset SLE (cSLE). METHODS: Attainment of three adult-SLE derived definitions of LDA (LLDAS, LA, Toronto-LDA), and four definitions of remission (clinical-SLEDAI-defined remission on/off treatment, pBILAG-defined remission on/off treatment) was assessed in UK JSLE Cohort Study patients longitudinally. Prentice-Williams-Petersen gap recurrent event models assessed the impact of LDA/remission attainment on severe flare/new damage. RESULTS: LLDAS, LA and Toronto-LDA targets were reached in 67%, 73% and 32% of patients, after a median of 18, 15 or 17 months, respectively. Cumulatively, LLDAS, LA and Toronto-LDA was attained for a median of 23%, 31% and 19% of total follow-up-time, respectively. Remission on-treatment was more common (61% cSLEDAI-defined, 42% pBILAG-defined) than remission off-treatment (31% cSLEDAI-defined, 21% pBILAG-defined). Attainment of all target states, and disease duration (>1 year), significantly reduced the hazard of severe flare (P < 0.001). As cumulative time in each target increased, hazard of severe flare progressively reduced. LLDAS attainment reduced the hazard of severe flare more than LA or Toronto-LDA (P < 0.001). Attainment of LLDAS and all remission definitions led to a statistically comparable reduction in the hazards of severe flare (P > 0.05). Attainment of all targets reduced the hazards of new damage (P < 0.05). CONCLUSIONS: This is the first study demonstrating that adult-SLE-derived definitions of LDA/remission are achievable in cSLE, significantly reducing risk of severe flare/new damage. Of the LDA definitions, LLDAS performed best, leading to a statistically comparable reduction in the hazards of severe flare to attainment of clinical remission.

Neuropsychiatric involvement in juvenile-onset systemic lupus erythematosus: Data from the UK Juvenile-onset systemic lupus erythematosus cohort study.

INTRODUCTION: Juvenile-onset systemic lupus erythematosus (JSLE) is a rare autoimmune/inflammatory disease with significant morbidity and mortality. Neuropsychiatric (NP) involvement is a severe complication, encompassing a heterogeneous range of neurological and psychiatric manifestations. METHODS: Demographic, clinical, and laboratory features of NP-SLE were assessed in participants of the UK JSLE Cohort Study, and compared to patients in the same cohort without NP manifestations. RESULTS: A total of 428 JSLE patients were included in this study, 25% of which exhibited NP features, half of them at first visit. Most common neurological symptoms among NP-JSLE patients included headaches (78.5%), mood disorders (48.6%), cognitive impairment (42%), anxiety (23.3%), seizures (19.6%), movement disorders (17.7%), and cerebrovascular disease (14.9%). Peripheral nervous system involvement was recorded in 7% of NP-SLE patients. NP-JSLE patients more frequently exhibited thrombocytopenia (<100 × 109/L) (p = 0.04), higher C-reactive protein levels (p = 0.01), higher global pBILAG score at first visit (p < 0.001), and higher SLICC damage index score at first (p = 0.02) and last (p < 0.001) visit when compared to JSLE patients without NP involvement. CONCLUSIONS: A significant proportion of JSLE patients experience NP involvement (25%). Juvenile-onset NP-SLE most commonly affects the CNS and is associated with increased overall disease activity and damage.

Limited sensitivity and specificity of the ACR/EULAR-2019 classification criteria for SLE in JSLE?-observations from the UK JSLE Cohort Study.

OBJECTIVES: This study aimed to test the performance of the new ACR and EULAR criteria, that include ANA positivity as entry criterion, in JSLE. METHODS: Performance of the ACR/EULAR-2019 criteria were compared with Systemic Lupus International Collaborating Clinics (SLICC-2012), using data from children and young people (CYP) in the UK JSLE Cohort Study (n = 482), with the ACR-1997 criteria used as reference standard. An unselected cohort of CYP positive for ANA (n = 129) was used to calculate positive/negative predictive values of the criteria. RESULTS: At both first and last visits, the number of patients fulfilling the different classification criteria varied significantly (P < 0.001). The sensitivity of the SLICC-2012 criteria was higher when compared with that of the ACR/EULAR-2019 criteria at first and last visits (98% vs 94% for first visit, and 98% vs 96% for last visit; P < 0.001), when all available CYP were considered. The ACR/EULAR-2019 criteria were more specific when compared with the SLICC-2012 criteria (77% vs 67% for first visit, and 81% vs 71% for last visit; P < 0.001). Significant differences between the classification criteria were mainly caused by the variation in ANA positivity across ages. In the unselected cohort of ANA-positive CYP, the ACR/EULAR-2019 criteria produced the highest false-positive classification (6/129, 5%). CONCLUSION: In CYP, the ACR/EULAR-2019 criteria are not superior to those of the SLICC-2012 or ACR-1997 criteria. If classification criteria are designed to include CYP and adult populations, paediatric rheumatologists should be included in the consensus and evaluation process, as seemingly minor changes can significantly affect outcomes.

Clinical and laboratory phenotypes in juvenile-onset Systemic Lupus Erythematosus across ethnicities in the UK.

Systemic lupus erythematosus (SLE) is a systemic autoimmune/inflammatory disease. Patients diagnosed with juvenile-onset SLE (jSLE), when compared to individuals with adult-onset SLE, develop more severe organ involvement, increased disease activity and greater tissue and organ damage. In adult-onset SLE, clinical characteristics, pathomechanisms, disease progression and outcomes do not only vary between individuals and age groups, but also ethnicities. However, in children and young people, the influence of ethnicity on disease onset, phenotype and outcome has not been investigated in detail. In this study, we investigated clinical and laboratory characteristics in pediatric SLE patients from different ethnic backgrounds (White Caucasian, Asian, Black African/Caribbean) accessing data from a national cohort of jSLE patients (the UK JSLE Cohort Study). Among jSLE patients in the UK, ethnicity affects both the disease's clinical course and outcomes. At diagnosis, Black African/Caribbean jSLE patients show more "classical" laboratory and clinical features when compared to White Caucasian or Asian patients. Black African/Caribbean jSLE patients exhibit more renal involvement and more frequently receive cyclophosphamide and rituximab. Studies targeting ethnicity-specific contributors to disease expression and phenotypes are necessary to improve our pathophysiological understanding, diagnosis and treatment of jSLE.

Pharmacological interventions for chronic pain in children: an overview of systematic reviews.

We know little about the safety or efficacy of pharmacological medicines for children and adolescents with chronic pain, despite their common use. Our aim was to conduct an overview review of systematic reviews of pharmacological interventions that purport to reduce pain in children with chronic noncancer pain (CNCP) or chronic cancer-related pain (CCRP). We searched the Cochrane Database of Systematic Reviews, Medline, EMBASE, and DARE for systematic reviews from inception to March 2018. We conducted reference and citation searches of included reviews. We included children (0-18 years of age) with CNCP or CCRP. We extracted the review characteristics and primary outcomes of ≥30% participant-reported pain relief and patient global impression of change. We sifted 704 abstracts and included 23 systematic reviews investigating children with CNCP or CCRP. Seven of those 23 reviews included 6 trials that involved children with CNCP. There were no randomised controlled trials in reviews relating to reducing pain in CCRP. We were unable to combine data in a meta-analysis. Overall, the quality of evidence was very low, and we have very little confidence in the effect estimates. The state of evidence of randomized controlled trials in this field is poor; we have no evidence from randomised controlled trials for pharmacological interventions in children with cancer-related pain, yet cannot deny individual children access to potential pain relief. Prospero ID: CRD42018086900.

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.

Multi-centre national audit of juvenile localised scleroderma: describing current UK practice in disease assessment and management.

OBJECTIVE: To describe current United Kingdom practice in assessment and management of patients with juvenile localised scleroderma (JLS) compared to Paediatric Rheumatology European Society (PRES) scleroderma working party recommendations. METHODS: Patients were included if they were diagnosed with JLS and were under the care of paediatric rheumatology between 04/2015-04/2016. Retrospective data was collected in eleven UK centres using a standardised proforma and collated centrally. RESULTS: 149 patients were included with a median age of 12.5 years. The outcome measures recommended by the PRES scleroderma working party were not utilised widely. The localised scleroderma cutaneous assessment tool was only used in 37.6% of patients. Screening for extracutaneous manifestations did not meet recommendations that patients with head involvement have regular screening for uveitis and baseline magnetic resonance imaging (MRI) brain: only 38.5% of these patients were ever screened for uveitis; 71.2% had a MRI brain. Systemic treatment with disease-modifying anti-rheumatic drugs (DMARDs) or biologics was widely used (96.0%). In keeping with the recommendations, 95.5% of patients were treated with methotrexate as first-line therapy. 82.6% received systemic corticosteroids and 34.2% of patients required two or more DMARDs/biologics, highlighting the significant treatment burden. Second-line treatment was mycophenolate mofetil in 89.5%. CONCLUSION: There is wide variation in assessment and screening of patients with JLS but a consistent approach to systemic treatment within UK paediatric rheumatology. Improved awareness of PRES recommendations is required to ensure standardised care. As recommendations are based on low level evidence and consensus opinion, further studies are needed to better define outcome measures and treatment regimens for JLS.

Cognitive Biases in Children and Adolescents With Chronic Pain: A Review of Findings and a Call for Developmental Research.

Cognitive biases that emphasize bodily harm, injury, and illness could play a role in the maintenance of chronic pain by facilitating fear and avoidance. Whereas extensive research has established attention, interpretation, and memory biases in adults with chronic pain, far less is known about these same biases in children and adolescents with pain. Studying cognitive biases in attention, interpretation, and memory in relation to pain occurring in youth is important because youth is a time when pain can first become chronic, and when relationships between cognitive biases and pain outcomes emerge and stabilize. Thus, youth potentially offers a time window for the prevention of chronic pain problems. In this article, we summarize the growing corpus of data that have measured cognitive biases in relation to pediatric pain. We conclude that although biases in attention, interpretation, and memory characterize children and adolescents with varying pain experiences, questions regarding the direction, magnitude, nature, and role of these biases remain. We call for independent extension of cognitive bias research in children and adolescents, using well powered longitudinal studies with wide age ranges and psychometrically sound experimental measures to clarify these findings and any developmental trends in the links between cognitive biases and pain outcomes. PERSPECTIVE: This article provides a rationale for the theoretical and practical importance of studying the role of cognitive biases in children and adolescents with chronic pain, which has to date, been relatively understudied. Existing findings are reviewed critically, and recommendations for future research are offered.

Paracetamol (acetaminophen) for chronic non-cancer pain in children and adolescents.

BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past, pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol as priority areas) in order to review the evidence for children's pain utilising pharmacological interventions in children and adolescents.As the leading cause of morbidity in children and adolescents in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications: nociceptive, neuropathic, idiopathic, visceral, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, and other unknown reasons.Paracetamol (acetaminophen) is one of the most widely used analgesics in both adults and children. The recommended dosage in the UK, Europe, Australia, and the USA for children and adolescents is generally 10 to 15 mg/kg every four to six hours, with specific age ranges from 60 mg (6 to 12 months old) up to 500 to 1000 mg (over 12 years old). Paracetamol is the only recommended analgesic for children under 3 months of age. Paracetamol has been proven to be safe in appropriate and controlled dosages, however potential adverse effects of paracetamol if overdosed or overused in children include liver and kidney failure. OBJECTIVES: To assess the analgesic efficacy and adverse events of paracetamol (acetaminophen) used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, and searched online clinical trial registries. SELECTION CRITERIA: Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing paracetamol with placebo or an active comparator. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and numbers needed to treat, using standard methods where data were available. We assessed GRADE (Grading of Recommendations Assessment, Development and Evaluation) and planned to create a 'Summary of findings' table. MAIN RESULTS: No studies were eligible for inclusion in this review. We rated the quality of the evidence as very low. We downgraded the quality of evidence by three levels due to the lack of data reported for any outcome. AUTHORS' CONCLUSIONS: There was no evidence from randomised controlled trials to support or refute the use of paracetamol (acetaminophen) to treat chronic non-cancer pain in children and adolescents. We are unable to comment about efficacy or harm from the use of paracetamol to treat chronic non-cancer pain in children and adolescents.We know from adult randomised controlled trials that paracetamol, can be effective, in certain doses, and in certain pain conditions (not always chronic).This means that no conclusions could be made about efficacy or harm in the use of paracetamol (acetaminophen) to treat chronic non-cancer pain in children and adolescents.

Non-steroidal anti-inflammatory drugs (NSAIDs) for chronic non-cancer pain in children and adolescents.

BACKGROUND: Pain is a common feature of childhood and adolescence around the world, and for many young people, that pain is chronic. The World Health Organization guidelines for pharmacological treatments for children's persisting pain acknowledge that pain in children is a major public health concern of high significance in most parts of the world. While in the past pain was largely dismissed and was frequently left untreated, views on children's pain have changed over time, and relief of pain is now seen as important.We designed a suite of seven reviews on chronic non-cancer pain and cancer pain (looking at antidepressants, antiepileptic drugs, non-steroidal anti-inflammatory drugs, opioids, and paracetamol) in order to review the evidence for children's pain utilising pharmacological interventions.As the leading cause of morbidity in the world today, chronic disease (and its associated pain) is a major health concern. Chronic pain (that is pain lasting three months or longer) can arise in the paediatric population in a variety of pathophysiological classifications (nociceptive, neuropathic, or idiopathic) from genetic conditions, nerve damage pain, chronic musculoskeletal pain, and chronic abdominal pain, as well as for other unknown reasons.Non-steroidal anti-inflammatory drugs (NSAIDs) are used to treat pain, reduce fever, and for their anti-inflammation properties. They are commonly used within paediatric pain management. Non-steroidal anti-inflammatory drugs are currently licensed for use in Western countries, however they are not approved for infants under three months old. The main adverse effects include renal impairment and gastrointestinal issues. Common side effects in children include diarrhoea, headache, nausea, constipation, rash, dizziness, and abdominal pain. OBJECTIVES: To assess the analgesic efficacy and adverse events of NSAIDs used to treat chronic non-cancer pain in children and adolescents aged between birth and 17 years, in any setting. SEARCH METHODS: We searched the Cochrane Central Register of Controlled Trials (CENTRAL) via the Cochrane Register of Studies Online, MEDLINE via Ovid, and Embase via Ovid from inception to 6 September 2016. We also searched the reference lists of retrieved studies and reviews, as well as online clinical trial registries. SELECTION CRITERIA: Randomised controlled trials, with or without blinding, of any dose and any route, treating chronic non-cancer pain in children and adolescents, comparing any NSAID with placebo or an active comparator. DATA COLLECTION AND ANALYSIS: Two review authors independently assessed studies for eligibility. We planned to use dichotomous data to calculate risk ratio and number needed to treat for one additional event, using standard methods. We assessed GRADE and created three 'Summary of findings' tables. MAIN RESULTS: We included seven studies with a total of 1074 participants (aged 2 to 18 years) with chronic juvenile polyarthritis or chronic juvenile rheumatoid arthritis. All seven studies compared an NSAID with an active comparator. None of the studies were placebo controlled. No two studies investigated the same type of NSAID compared with another. We were unable to perform a meta-analysis.Risk of bias varied. For randomisation and allocation concealment, one study was low risk and six studies were unclear risk. For blinding of participants and personnel, three studies were low risk and four studies were unclear to high risk. For blinding of outcome assessors, all studies were unclear risk. For attrition, four studies were low risk and three studies were unclear risk. For selective reporting, four studies were low risk, two studies were unclear risk, and one study was high risk. For size, three studies were unclear risk and four studies were high risk. For other potential sources of bias, seven studies were low risk. Primary outcomesThree studies reported participant-reported pain relief of 30% or greater, showing no statistically significant difference in pain scores between meloxicam and naproxen, celecoxib and naproxen, or rofecoxib and naproxen (P > 0.05) (low-quality evidence).One study reported participant-reported pain relief of 50% or greater, showing no statistically significant difference in pain scores between low-dose meloxicam (0.125 mg/kg) and high-dose meloxicam (0.25 mg/kg) when compared to naproxen 10 mg/kg (P > 0.05) (low-quality evidence).One study reported Patient Global Impression of Change, showing 'very much improved' in 85% of ibuprofen and 90% of aspirin participants (low-quality evidence). Secondary outcomesAll seven studies reported adverse events. Participants reporting an adverse event (one or more per person) by drug were: aspirin 85/202; fenoprofen 28/49; ibuprofen 40/45; indomethacin 9/30; ketoprofen 9/30; meloxicam 18/47; naproxen 44/202; and rofecoxib 47/209 (very low-quality evidence).All seven studies reported withdrawals due to adverse events. Participants withdrawn due to an adverse event by drug were: aspirin 16/120; celecoxib 10/159; fenoprofen 0/49; ibuprofen 0/45; indomethacin 0/30; ketoprofen 0/30; meloxicam 10/147; naproxen 17/285; and rofecoxib 3/209 (very low-quality evidence).All seven studies reported serious adverse events. Participants experiencing a serious adverse event by drug were: aspirin 13/120; celecoxib 5/159; fenoprofen 0/79; ketoprofen 0/30; ibuprofen 4/45; indomethacin 0/30; meloxicam 11/147; naproxen 10/285; and rofecoxib 0/209 (very low-quality evidence).There were few or no data for our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning as defined by validated scales; and quality of life as defined by validated scales (very low-quality evidence).We rated the overall quality of the evidence (GRADE rating) for our primary and secondary outcomes as very low because there were limited data from studies and no opportunity for a meta-analysis. AUTHORS' CONCLUSIONS: We identified only a small number of studies, with insufficient data for analysis.As we could undertake no meta-analysis, we are unable to comment about efficacy or harm from the use of NSAIDs to treat chronic non-cancer pain in children and adolescents. Similarly, we cannot comment on our remaining secondary outcomes: Carer Global Impression of Change; requirement for rescue analgesia; sleep duration and quality; acceptability of treatment; physical functioning; and quality of life.We know from adult randomised controlled trials that some NSAIDs, such as ibuprofen, naproxen, and aspirin, can be effective in certain chronic pain conditions.

Negative Interpretation Bias and the Experience of Pain in Adolescents.

UNLABELLED: Negative interpretation bias, the tendency to appraise ambiguous situations in a negative or threatening way, has been suggested to be important for the development of adult chronic pain. To our knowledge, this is the first study to examine the role of a negative interpretation bias in adolescent pain. We first developed and piloted a novel task that measures the tendency for adolescents to interpret ambiguous situations as indicative of pain and bodily threat. Using this task in a separate community sample of adolescents (N = 115), we then found that adolescents who catastrophize about pain, as well as those who reported more pain issues in the preceding 3 months, were more likely to endorse negative interpretations, and less likely to endorse benign interpretations, of ambiguous situations. This interpretation pattern was not, however, specific for situations regarding pain and bodily threat, but generalized across social situations as well. We also found that a negative interpretation bias, specifically in ambiguous situations that could indicate pain and bodily threat, mediated the association between pain catastrophizing and recent pain experiences. Findings may support one potential cognitive mechanism explaining why adolescents who catastrophize about pain often report more pain. PERSPECTIVE: This article presents a new adolescent measure of interpretation bias. We found that the tendency to interpret ambiguous situations as indicative of pain and bodily threat may be one potential cognitive mechanism explaining why adolescents who catastrophize about pain report more pain, thus indicating a potential novel intervention target.

Staring us in the face? An embodied theory of innate face preference.

Human expertise in face perception grows over development, but even within minutes of birth, infants exhibit an extraordinary sensitivity to face-like stimuli. The dominant theory accounts for innate face detection by proposing that the neonate brain contains an innate face detection device, dubbed 'Conspec'. Newborn face preference has been promoted as some of the strongest evidence for innate knowledge, and forms a canonical stage for the modern form of the nature-nurture debate in psychology. Interpretation of newborn face preference results has concentrated on monocular stimulus properties, with little mention or focused investigation of potential binocular involvement. However, the question of whether and how newborns integrate the binocular visual streams bears directly on the generation of observable visual preferences. In this theoretical paper, we employ a synthetic approach utilizing robotic and computational models to draw together the threads of binocular integration and face preference in newborns, and demonstrate cases where the former may explain the latter. We suggest that a system-level view considering the binocular embodiment of newborn vision may offer a mutually satisfying resolution to some long-running arguments in the polarizing debate surrounding the existence and causal structure of newborns' 'innate knowledge' of faces.

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.