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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Tofacitinib is an oral Janus kinase inhibitor. This trial assessed the efficacy and safety of tofacitinib versus placebo in patients with polyarticular course juvenile idiopathic arthritis (JIA).
...This double-blind, withdrawal phase 3 trial enrolled patients with polyarticular course JIA (extended oligoarthritis, rheumatoid factor-positive or rheumatoid factor-negative polyarthritis, or systemic JIA without active systemic features) aged 2 years to younger than 18 years, and was done at 64 centres of the Paediatric Rheumatology International Trials Organisation and Pediatric Rheumatology Collaborative Study Group networks in 14 countries. Patients with psoriatic arthritis or enthesitis-related arthritis were enrolled for exploratory endpoints. During part 1 of the study, patients received oral open-label tofacitinib (weight-based doses; 5 mg twice daily or lower) for 18 weeks. Patients achieving at least JIA/American College of Rheumatology 30 response were randomly assigned (1:1) using an Interactive Response Technology system to continue tofacitinib or switch to placebo in part 2 of the study for 26 weeks. The primary endpoint was JIA flare rate by week 44 in part 2 in patients with polyarticular course JIA; the intention-to-treat principle was applied. Safety was evaluated throughout part 1 and part 2 of the study in all patients who received one dose or more of study medication. This trial is registered with ClinicalTrials.gov, NCT02592434.
Between June 10, 2016, and May 16, 2019, of 225 patients enrolled, 184 (82%) patients had polyarticular course JIA, 20 (9%) had psoriatic arthritis, and 21 (9%) had enthesitis-related arthritis. 147 (65%) of 225 patients received concomitant methotrexate. In part 2, 142 patients with polyarticular course JIA were assigned to tofacitinib (n=72) or placebo (n=70). Flare rate by week 44 was significantly lower with tofacitinib (21 29% of 72 patients) than with placebo (37 53% of 70 patients; hazard ratio 0·46, 95% CI 0·27–0·79; p=0·0031). In part 2 of the study, adverse events occurred in 68 (77%) of 88 patients receiving tofacitinib and 63 (74%) of 85 in the placebo group. Serious adverse events occurred in one (1%) and two (2%), respectively. In the entire tofacitinib exposure period, 107 (48%) of 225 patients had infections or infestations. There were no deaths during this study.
The results of this pivotal trial show that tofacitinib is an effective treatment in patients with polyarticular course JIA. New oral therapies are particularly relevant for children and adolescents, who might prefer to avoid injections.
Pfizer.
Objective
The objective of this article is to examine the quality, content, and readability of information and resources in the English language and accessible on the internet by pediatric patients ...with systemic lupus erythematosus (SLE) and their families in North America.
Methods
Keywords relevant to SLE were generated by an undergraduate student, a first-year medical student, and a third-year pediatric resident, and a search was conducted across five commonly used search engines. Quality of information found was evaluated independently by an undergraduate student, a graduate student, a first-year medical student, and a third-year pediatric resident using the DISCERN tool. Two pediatric rheumatologists assessed website accuracy and completeness. Readability of websites was determined using the Flesch-Kincaid grade level and Reading Ease score.
Results
Out of 2000 websites generated in the search, only 34 unique websites met inclusion criteria. Only 16 of these websites had DISCERN scores above 50% (fair quality). Overall quality of website information was fair with mean ±standard deviation (SD) DISCERN quality score of 44 ± 7 (range: 30–56). Only nine websites of 34 had DISCERN scores above 50 (>66%, indicating greater quality) and were further assessed for completeness. Flesch-Kincaid grade level was 11 ± 1 (mean±SD) and reading ease score was 39 ± 10 (mean±SD, range of 11–61).
Conclusion
Our study highlights the need for more complete, readable information regarding the unique needs of pediatric patients with childhood-onset SLE and their families.
Objectives To validate the previously proposed classification criteria for Henoch–Schönlein purpura (HSP), childhood polyarteritis nodosa (c-PAN), c-Wegener granulomatosis (c-WG) and c-Takayasu ...arteritis (c-TA). Methods Step 1: retrospective/prospective web-data collection for children with HSP, c-PAN, c-WG and c-TA with age at diagnosis ≤18 years. Step 2: blinded classification by consensus panel of a representative sample of 280 cases. Step 3: statistical (sensitivity, specificity, area under the curve and κ-agreement) and nominal group technique consensus evaluations. Results 827 patients with HSP, 150 with c-PAN, 60 with c-WG, 87 with c-TA and 52 with c-other were compared with each other. A patient was classified as HSP in the presence of purpura or petechiae (mandatory) with lower limb predominance plus one of four criteria: (1) abdominal pain; (2) histopathology (IgA); (3) arthritis or arthralgia; (4) renal involvement. Classification of c-PAN required a systemic inflammatory disease with evidence of necrotising vasculitis OR angiographic abnormalities of medium-/small-sized arteries (mandatory criterion) plus one of five criteria: (1) skin involvement; (2) myalgia/muscle tenderness; (3) hypertension; (4) peripheral neuropathy; (5) renal involvement. Classification of c-WG required three of six criteria: (1) histopathological evidence of granulomatous inflammation; (2) upper airway involvement; (3) laryngo-tracheo-bronchial involvement; (4) pulmonary involvement (x-ray/CT); (5) antineutrophilic cytoplasmic antibody positivity; (6) renal involvement. Classification of c-TA required typical angiographic abnormalities of the aorta or its main branches and pulmonary arteries (mandatory criterion) plus one of five criteria: (1) pulse deficit or claudication; (2) blood pressure discrepancy in any limb; (3) bruits; (4) hypertension; (5) elevated acute phase reactant. Conclusion European League Against Rheumatism/Paediatric Rheumatology International Trials Organisation/Paediatric Rheumatology European Society propose validated classification criteria for HSP, c-PAN, c-WG and c-TA with high sensitivity/specificity.
Objectives
The objective of this report is to use diffusion-tensor imaging (DTI) for investigating white-matter connectivity changes associated with neurocognitive dysfunction in childhood-onset ...lupus (cSLE-NCD) as measured by formal neuropsychological testing.
Methods
DTI was performed in six individuals with (cSLE-NCD) and nine without neurocognitive dysfunction (cSLE-noNCD) as well as 14 healthy controls. Presence of neurocognitive deficits was identified by formal neuropsychological testing. The brain was divided into 116 regions, and pairwise connectivity (defined as the number of streamlines with an endpoint in each of those regions) and streamline density (defined as the number of streamlines passing through a region regardless of endpoints) were evaluated. Group comparisons were made for regional and global measures of streamline density and pairwise connectivity.
Results
A significant decrease in global streamline density was observed in the cSLE-NCD vs. control group (1189 vs. 1305 p = 0.002) and vs. cSLE-noNCD (1189 vs 1320 p = 0.001). The cSLE-noNCD and control groups had similar streamline density. A similar pattern for pairwise connectivity was observed with a significant decrease in the cSLE-NCD group (217) versus the cSLE-noNCD (236; p = 0.013) and control group (238; p = 0.004). Regional measures of pairwise connectivity displayed mixed results.
Conclusions
The analysis of DTI in this pilot study shows cSLE-NCD is associated with global loss of streamline density and pairwise connectivity, suggesting breakdown of the structural network. These results complement previously reported functional and volumetric findings that suggest cSLE-NCD is associated with measurable changes in gray and white matter. If confirmed in larger cohorts, DTI abnormalities could be used as imaging biomarkers of cSLE-NCD.
Objective
To investigate clinical manifestations of juvenile systemic sclerosis (SSc; scleroderma), including disease characteristics and patient quality of life, using the multinational Childhood ...Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry.
Methods
Patients with juvenile SSc were prospectively enrolled between 2010 and 2013. The diagnosis of juvenile SSc was determined by the enrolling pediatric rheumatologist, with the requirement for disease onset prior to age 18 years. Collected data included demographics, disease characteristics, medication exposure, and quality of life metrics.
Results
In total, 64 patients with juvenile SSc were enrolled a median of 3.6 years after disease onset, which occurred at a median age of 10.3 years. The most common organ manifestations were dermatologic and vascular, followed by musculoskeletal, gastrointestinal, and pulmonary; in 38% of patients, ≥4 organ systems were affected. Patients with juvenile SSc had significantly more disability at enrollment compared with CARRA Legacy Registry patients with juvenile idiopathic arthritis, dermatomyositis, or systemic lupus erythematosus. Although physician‐reported measures correlated most closely with arthritis, dermatologic manifestations, and pulmonary manifestations, poor patient‐reported measures were associated with gastrointestinal involvement. During >50 person‐years of follow‐up, most organ manifestations remained stable, and no mortality or development of new solid organ involvement after enrollment was reported.
Conclusion
In the first multicenter prospective cohort of patients with juvenile SSc in North America, the disease burden was high: multiorgan manifestations were common, and functional disability was greater than that observed in patients with other childhood‐onset rheumatic diseases. Gastrointestinal involvement had the greatest impact on quality of life.
Objective
Prompt treatment for lupus is important to prevent morbidity. A potential barrier to early treatment of pediatric lupus is delayed presentation to a pediatric rheumatologist. To better ...understand factors contributing to delayed presentation among pediatric lupus patients, we examined differences in demographic and clinical characteristics of lupus patients within the Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry with regard to time between symptom onset and presentation to a pediatric rheumatologist.
Methods
We analyzed data from 598 CARRA Legacy Registry participants for differences between those who presented early (within <1 month of symptom onset), between 1–3 months (typical presentation), with moderate delays (3–12 months), and with severe delays (≥1 year). Factors associated with early presentation, moderate delay, and severe delay were determined by multinomial logistic regression.
Results
Forty‐four percent of patients presented early, while 23% had moderate delays and 9% had severe delays. Family history of lupus, absence of discoid rash, and location in a state with a higher density of pediatric rheumatologists were associated with earlier presentation. Younger age, low household income (<$25,000 per year), and a family history of lupus were associated with severe delay.
Conclusion
Delays to care ≥1 year exist in a notable minority of pediatric lupus patients from the CARRA Legacy Registry. In this large and diverse sample of patients, access to care and family resources played an important role in predicting time to presentation to a pediatric rheumatologist.
Objective
Ultraviolet (UV) radiation is considered to be an important environmental factor in the clinical course of children with juvenile dermatomyositis (DM). We aimed to evaluate the association ...between UV radiation and severe disease outcomes in juvenile DM.
Methods
This is a cross‐sectional study of patients with juvenile DM enrolled in the US multicenter Childhood Arthritis and Rheumatology Research Alliance (CARRA) Legacy Registry from 2010 to 2015. The mean UV index (UVI) in the calendar month prior to symptom onset in each subject's zip code was calculated from daily satellite solar noon measurements. Multivariable logistic regression was used to model the relationship between the mean UVI and calcinosis as well as other outcomes of severe disease. Covariates included sex, race, age, time to diagnosis, disease duration, and latitude.
Results
In a multivariable model, there was no association between the mean UVI and calcinosis. African American race was associated with a 3‐fold greater odds of calcinosis. However, there was a significant statistical interaction between race and mean UVI. Accounting for this interaction, the odds of calcinosis markedly decreased in African American subjects and steadily increased in non–African American subjects over a range of increasing the mean UVI. Higher mean UVI was associated with decreased odds of using biologics or nonmethotrexate disease‐modifying antirheumatic drugs and skin ulceration.
Conclusion
We described a novel association between UV radiation, calcinosis, and race in a large cohort of patients with juvenile DM. This study furthers our knowledge of the role of UV radiation in the clinical course of juvenile DM and highlights the complex interplay between genes and environment in the clinical phenotypes and development of calcinosis in children with juvenile DM.
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
Objective
This study evaluated the effects of obesity on health-related quality of life (HRQOL) measures in juvenile-onset systemic lupus erythematosus (jSLE).
Methods
Obesity was defined as a body ...mass index (BMI) ≥95th percentile according to the Sex-specific Center for Disease Control BMI-For-Age Charts and determined in a multicenter cohort of jSLE patients. In this secondary analysis, the domain and summary scores of the Pediatric Quality of Life (PedsQL) Inventory and the Child Health Questionnaire (CHQ) of obese jSLE patients were compared to those of non-obese jSLE patients as well as historical obese and non-obese healthy controls. Mixed-effects modeling was performed to evaluate the relationship between obesity and HRQOL measures.
Results
Among the 202 jSLE patients, 25% (n = 51) were obese. Obesity had a significant negative impact on HRQOL in jSLE, even after adjusting for differences in current corticosteroid use, disease activity, disease damage, gender and race between groups. Obese jSLE patients had lower physical functioning compared to non-obese jSLE patients, and to non-obese and obese healthy controls. Compared to their non-obese counterparts, obese jSLE patients also had worse school functioning, more pain, worse social functioning and emotional functioning. Parents of obese jSLE patients worry more. The CHQ scores for obese jSLE patients were also worse compared to non-obese jSLE patients in several other domains.
Conclusion
Our study demonstrates the detrimental effects of obesity on patient-reported outcomes in jSLE. This supports the importance of weight management for the therapeutic plan of jSLE.
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