Purpose
A key limitation to widespread adoption of patient-reported outcome (PRO) measures is the lack of interpretability of scores. We aim to identify clinical severity thresholds to distinguish ...categories of no problems, mild, moderate, and severe along the PROMIS® Pediatric T-score metric for measures of anxiety, mobility, fatigue, and depressive symptoms for use in populations with juvenile idiopathic arthritis (JIA) and childhood-onset systemic lupus erythematosus (cSLE).
Methods
We used a modified standard setting methodology from educational testing to identify clinical severity thresholds (clinical cut scores). Using item response theory-based parameters from PROMIS item banks, we developed a series of clinical vignettes that represented different severity or ability levels along the PROMIS Pediatric T-score metric. In stakeholder workshops, participants worked individually and together to reach consensus on clinical cut scores. Median cut-score placements were taken when consensus was not reached. Focus groups were recorded and qualitative analysis was conducted to identify decision-making processes.
Results
Nine adolescents (age 13–17 years) with JIA (33% female) and their caregivers, five adolescents (age 14–16 years) with cSLE (100% female) and their caregivers, and 12 pediatric rheumatologists (75% female) participated in bookmarking workshops. Placement of thresholds for bookmarks was highly similar across stakeholder groups (differences from 0 to 5 points on the PROMIS t-score metric) for all but one bookmark placement.
Conclusion
This study resulted in clinical thresholds for severity categories for PROMIS Pediatric measures of anxiety, mobility, fatigue, and depressive symptoms, providing greater interpretability of scores in JIA and cSLE populations.
Summary
Background
Children with discoid lupus erythematosus (DLE) are at risk for disfigurement and progression to systemic lupus erythematosus (SLE). Consensus is lacking regarding optimal care for ...children with DLE.
Objectives
The aim of this study was to compare practice patterns among paediatric dermatologists/rheumatologists treating paediatric DLE.
Methods
An online survey was sent to 292 paediatric rheumatologists in the Childhood Arthritis and Rheumatology Research Alliance and 200 paediatric dermatologists in the Pediatric Dermatology Research Alliance. Consensus was defined as ≥ 70% agreement.
Results
Survey response rates were 38% (76 of 200) for dermatology and 21% (60 of 292) for rheumatology. Both specialties agreed that screening labs should include complete blood counts with differential, urinalysis, complement levels, erythrocyte sedimentation rate, antinuclear antibody and other autoantibodies, hepatic function and renal function/electrolytes. Both specialties agreed that arthritis or nephritis should prompt intensified evaluation for SLE. No other patient features achieved consensus as disease‐modifying risk factors. Hydroxychloroquine was agreed upon as first‐line systemic therapy, but consensus was lacking for second‐ or third‐line treatment.
Conclusions
We found few areas of consensus and significant practice differences between paediatric dermatologists and rheumatologists treating DLE. Knowledge gaps include risk factors for SLE, optimal screening and treatment of refractory skin disease.
What's already known about this topic?
Consensus for the evaluation and treatment of paediatric discoid lupus erythematosus (DLE) is lacking.
What does this study add?
Paediatric dermatologists/rheumatologists agree on some but not all aspects of work‐up and risk stratification for paediatric DLE.
Hydroxychloroquine was agreed upon as first‐line systemic therapy, but consensus was lacking for the management of refractory paediatric DLE.
Linked Comment: Ruth and Wine Lee. Br J Dermatol 2019; 181:662–663.
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Objective
The objective of this article is to describe and compare clinical features, treatment, and renal outcomes of children with membranous lupus nephritis (MLN), through analysis of a national ...multicenter registry.
Methods
Patients with pediatric systemic lupus erythematosus (SLE) and MLN from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry were included. Demographic, disease and medication-related data were collected between 2010 and 2014 from 59 CARRA Legacy Registry sites.
Results
A total of 132 individuals had MLN, either in isolation or in combination with proliferative LN. Seventy-four patients had pure MLN. The proportion of patients with daily corticosteroid treatment was similar among groups (96%, 91%, and 96%, for class III+V, IV+V, and V, respectively, p = 0.67). Proportion of individuals exposed to any disease-modifying antirheumatic drug (DMARD) or biologic was similar among the three groups (83%, 91%, 95% for class III+V, IV+V, and V, respectively, p = 0.189). Proportion of patients with decreased glomerular filtration rate (less than 90 ml/min/1.73 m2) was significantly different among groups (4%, 38%, and 4%, for class III+V, IV+V, and V, respectively, p < 0.0001).
Conclusion
This is the largest reported cohort of children with MLN. More research is needed to understand treatment practices for pediatric MLN, particularly decisions related to pharmacologic treatment of pure MLN. More work is also needed to identify prognostic factors and predictors of outcome for pediatric MLN. Future observational studies will be a first step toward understanding and formulating a standardized approach to treatment of pediatric membranous LN and allowing for the initiation of prospective comparative effectiveness studies and interventional trials.
BackgroundRecently, a dramatic increase in HER2 expression in the glomeruli and in the tubular compartment of patients with lupus nephritis was observed. A similar pattern was not seen in patients ...with IgA nephropathy, post-streptococcal glomerulonephritis or granulomatosis with polyangiitis. HER2 overexpression was also found in NZM2410 mice and it correlated with disease activity. In vitro, IRF1 and α-interferon increased HER2 expression in human mesangial cells and HER2 regulated the levels of miR-26a and miR-30b. These miRNAs control mesangial cell proliferation, by regulating the expression of several genes, including those controlling cell cycle. It was also found that urinary HER2 levels were increased in patients with active lupus nephritis in an adult cohort and correlated with the urine protein:creatinine ratio and with the levels of MCP-1 and VCAM-1.ObjectivesDetermine the role of HER2 as a urinary biomarker for lupus nephritis activity.MethodsThis is an interim analysis of a prospective, multicentric study, of patients with juvenile-onset systemic lupus erythematosus with biopsy-proven lupus nephritis. Urine samples were collected from patients at every clinical visit and also from age-sex matched controls. The samples were centrifuged and the supernatants were analyzed by enzyme-linked immunosorbent assays for HER2. Clinical data were also collected. The activity of lupus nephritis was measured using renal SLEDAI. Unpaired and paired t tests were used for the comparisons between samples. The relationship between HER2 and disease activity was defined by Pearson's correlation and linear regression.ResultsUrinary HER2 is significantly increased in children with lupus nephritis (N=15) when compared to controls (N=24) (p=0.003). Furthermore, our preliminary data from patients analyzed at different visits showed that HER2 levels tend to reflect disease activity.ConclusionsHER2 was significantly increased in the urine of children with lupus nephritis and its levels changed between visits, reflecting disease activity. Further studies are necessary to determine if HER2 levels can be clinically useful, namely if they can predict the occurrence of a flare. These findings also support the study of anti-HER2 drugs for cell proliferation control in lupus nephritis.ReferencesCosta Reis P, Russo PA, Zhang Z et al. The role of microRNAs and Human Epidermal Growth Factor Receptor 2 in Proliferative Lupus Nephritis. Arthritis Rheumatol. 2015 Sep;67(9).Disclosure of InterestNone declared
Practice‐based differences in paediatric DLE Arkin, L.; Buhr, K.; Brandling‐Bennett, H. ...
British journal of dermatology (1951),
October 2019, 2019-10-00, 20191001, Letnik:
181, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Summary
The term ‘lupus’ refers to a range of related disorders. Discoid lupus erythematosus (DLE) is a form of lupus in the skin, which is rare in children. It can lead to disfiguring scarring. Some ...patients develop systemic lupus (SLE), a type of lupus that affects the whole body, which can lead to damage to multiple organs. Small studies have suggested that 25 to 30% of children with DLE develop SLE over time, but risk factors for this are not known. Early diagnosis and treatment of SLE are helpful. This study used a survey approach to compare practice patterns between two medical specialties, academic rheumatologists and dermatologists, in the United States and Canada, caring for children with DLE. The study aimed to identify areas of agreement but also practice‐based differences between groups. Consensus (agreement) occurred when 70% or more of both specialties agreed. The authors found consensus that certain laboratory studies should be checked for all children at diagnosis of DLE. Both groups agreed that the presence of “other auto‐antibodies besides ANA”, arthritis, or nephritis were high‐risk features for SLE that should increase screening for systemic disease. There were no other agreed‐upon risk factors for SLE, including those that have previously been shown in adults with DLE. Both groups agreed that first‐line systemic therapy (whole body treatment) for widespread DLE should be hydroxychloroquine. The authors could not agree on which medications to use for resistant skin disease. Overall, the study found some areas of agreement but many areas of practice‐based difference. More data in children with DLE is necessary to determine best practice approaches. The authors are completing a type of study called a retrospective cohort study that may help to fill these gaps.
Linked Article: Arkin et al. Br J Dermatol 2019; 181:805–810
儿童 DLE 的基于实践的差异 Arkin, L.; Buhr, K.; Brandling‐Bennett, H. ...
British journal of dermatology (1951),
October 2019, 20191001, Letnik:
181, Številka:
4
Journal Article
Recenzirano
Summary
术语“红斑狼疮”指的是一系列相关疾病。盘状红斑狼疮 (DLE) 是一种在儿童中罕见的皮肤红斑狼疮。其可导致毁容性瘢痕。某些患者出现系统性红斑狼疮 (SLE),这是一种影响全身的红斑狼疮,其可导致多器官损害。多项小型研究表明,25 ‐ 30% 的 DLE 儿童患者随时间推移出现 SLE,但与此相关的风险因素尚不明确。SLE ...早期诊断和治疗很有帮助。本研究采用一种调查方法来比较美国和加拿大两个医学专业(学术型风湿科医师和皮肤科医师)为 DLE 儿童患者提供护理的实践模式。本研究的目的在于识别两组间的一致方面,以及基于实践的差异。若两个专业达到 70% 或更多的一致,则出现共识(一致)。作者发现了应在所有儿童诊断为 DLE 时查看某些实验室研究的共识。两组都同意,存在“除 ANA 以外的其他自身抗体”、关节炎或肾炎是 SLE 的高风险特性,对此应增加系统性疾病的筛查。没有其他一致同意的 SLE 风险因素,包括先前在 DLE 成人患者中显示的风险因素。两组都同意,泛发性 DLE 的一线系统性疗法(全身治疗)应为羟氯喹。作者未就哪些药物可用于治疗耐药性皮肤病达成一致。总而言之,本研究发现某些一致方面,但许多方面存在基于实践的差异。需要有关 DLE 儿童患者的更多数据来确定最佳实践方法。作者正在开展一项回顾性队列研究,该研究可能有助于填补这一空白。
Linked Article: Arkin et al. Br J Dermatol 2019; 181:805–810
Severe pain and impairments in functioning are commonly reported for youth with juvenile fibromyalgia. The prevalence and impact of pain in other diseases commonly managed in pediatric rheumatology ...comparatively have been rarely systematically studied. The objective of the current study was to determine the extent to which high levels of pain and functional limitations, and the strength of their association, are unique to youth with juvenile primary fibromyalgia syndrome/JPFS) relative to other pediatric rheumatic diseases.
Using data from 7753 patients enrolled in the multinational Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry, we compared the levels and association of pain and functional limitations between youth with JPFS and those with other rheumatic diseases.
Pain levels were rated highest among youth with JPFS (M = 6.4/10, SD = 2.4) and lowest for juvenile dermatomyositis (M = 1.7/10, SD = 2.2), with pain significantly higher in the JPFS group than any other pediatric rheumatic disease (effect sizes = .22 to 1.05). Ratings on measures of functioning and well-being also were significantly worse for patients with JPFS than patients with any other rheumatic disease (effect sizes = .62 to 1.06). The magnitude of association between pain intensity and functional disability, however, generally was higher in other rheumatic diseases than in JPFS. Pain was most strongly associated with functional limitations in juvenile dermatomyositis, juvenile idiopathic arthritis, and mixed connective tissue disease.
JPFS is unique among conditions seen in pediatric rheumatology with regard to ratings of pain and disability. However, pain appears to be comparably or more highly associated with level of functional impairment in other pediatric rheumatic diseases. Pain in childhood rheumatic disease thus would benefit from increased prioritization for research and treatment.
Global disease activity scores (gVAS) capture patient or family (PF) and physician (MD) assessments of disease. This study sought to measure discordance between PF and MD global activity scores in ...juvenile dermatomyositis (JDM), and determine factors associated with discordance.
Patients with JDM were included from the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry (N = 563). PF and MD gVAS were assessed for discordance, defined as a ≥ 2-point difference. Factors associated with discordant gVAS were compared in univariate analysis. Multivariable regression analysis was used to identify predictors of discordance.
Almost 40% (N = 219) of PF and MD gVAS were discordant. Among discordant scores, 68% of PF rated gVAS ≥2-points above MD, which was associated with calcinosis and lower quality of life and functional scores (p < 0.01). MD gVAS rated ≥2-points above PF in 32%, which was associated with abnormal laboratory results, weakness, arthritis, rash and other skin changes, and current intravenous steroid treatment (p < 0.01). In multivariate analysis, predictors for higher PF rating included calcinosis, lower quality of life and functional scores, while predictors for higher MD rating included rash, calcinosis, nailfold capillaroscopy changes, and current intravenous steroid treatment.
Discordance between PF and MD gVAS was common in this JDM cohort. Overall, higher PF rating was associated with poorer patient reported outcome (PRO) scores, while higher MD rating was associated with poorer objective measures. This suggests PF and MD assessments of gVAS may be measuring different aspects of disease, highlighting the importance of integrating PROs into clinical practice and research.
As part of the Atherosclerosis Prevention in Pediatric Lupus Erythematosus (APPLE) Trial, a prospective multicenter cohort of 221 children and adolescents with systemic lupus erythematosus (SLE) ...(mean age 15.7 years, 83% female) underwent baseline measurement of markers of cardiovascular risk, including fasting levels of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglycerides (TG), lipoprotein A (Lpa), homocysteine and high-sensitivity C-reactive protein (hs-CRP). A cross-sectional analysis of the baseline laboratory values and clinical characteristics of this cohort was performed. Univariable relationships between the cardiovascular markers of interest and clinical variables were assessed, followed by multivariable linear regression modeling. Mean levels of LDL, HDL, Lpa, TG, hs-CRP and homocysteine were in the normal or borderline ranges. In multivariable analysis, increased Systemic Lupus Erythematosus Disease Activity Index (SLEDAI), prednisone dose, and hypertension (HTN) were independently associated with higher LDL levels. Higher hs-CRP and creatinine clearance were independently related to lower HDL levels. Higher body mass index (BMI), prednisone dose, and homocysteine levels were independently associated with higher TG levels. Only Hispanic or non-White status predicted higher Lpa levels. Proteinuria, higher TG and lower creatinine clearance were independently associated with higher homocysteine levels, while use of multivitamin with folate predicted lower homocysteine levels. Higher BMI, lower HDL, and longer SLE disease duration, but not SLEDAI, were independently associated with higher hs-CRP levels. The R2 for these models ranged from 7% to 23%. SLE disease activity as measured by the SLEDAI was associated only with higher LDL levels and not with hs-CRP. Markers of renal injury (HTN, proteinuria, and creatinine clearance) were independently associated with levels of LDL, HDL, and homocysteine, highlighting the importance of renal status in the cardiovascular health of children and adolescents with SLE. Future longitudinal analysis of the APPLE cohort is needed to further examine these relationships.
The incidence of systemic lupus in children with discoid lupus is unknown.
This study assessed the baseline characteristics of patients with pediatric discoid lupus erythematosus (pDLE).
Medical ...records at 17 sites were reviewed for pediatric dermatology and rheumatology patients with discoid lupus erythematosus. The inclusion criteria were clinical and/or histopathologic diagnosis of discoid lupus erythematosus with an age at onset of <18 years. Baseline data were collected at the first documented visit. Outcomes included diagnosis of systemic lupus erythematosus (SLE) at the baseline visit using the 1997 American College of Rheumatology (primary) and the 2012 Systemic Lupus International Collaborating Clinics (secondary) criteria.
Of the >1500 charts reviewed, 438 patients met the inclusion criteria. The cohort was predominantly female (72%) and racially/ethnically diverse. A diagnosis of SLE at the baseline visit (pDLE + SLE) was rendered in 162 (37%) patients using the American College of Rheumatology and in 181 (41%) patients using the Systemic Lupus International Collaborating Clinics criteria. Patients with pDLE + SLE were older at the time of rash onset (median, 12.9 vs 8.9 years; P < .001), with shorter time from discoid lupus erythematosus onset to diagnosis, compared with patients with pDLE-only (median, 2 vs 7 months; P < .001). Patients with pDLE + SLE were more likely to be female (P = .004), with generalized discoid lupus erythematosus and clinically aggressive disease, including end-organ involvement, positive serologies, and higher- titer levels of antinuclear antibodies (P < .001).
Retrospective study.
A diagnosis of discoid lupus erythematosus in adolescence should prompt thorough screening for SLE.
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