Background
Systemic lupus erythematous (SLE) is a systemic autoimmune/inflammatory condition. Approximately 15–20% of patients develop symptoms before their 18th birthday and are diagnosed with ...juvenile-onset SLE (JSLE). Gender distribution, clinical presentation, disease courses and outcomes vary significantly between JSLE patients and individuals with adult-onset SLE. This study aimed to identify age-specific clinical and/or serological patterns in JSLE patients enrolled to the UK JSLE Cohort Study.
Methods
Patient records were accessed and grouped based on age at disease-onset: pre-pubertal (≤7 years), peri-pubertal (8–13 years) and adolescent (14–18 years). The presence of American College of Rheumatology (ACR) classification criteria, laboratory results, disease activity British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores and damage Systemic Lupus International Collaborating Clinics (SLICC) damage index were evaluated at diagnosis and last follow up.
Results
A total of 418 JSLE patients were included in this study: 43 (10.3%) with pre-pubertal disease onset; 240 (57.4%) with peri-pubertal onset and 135 (32.3%) were diagnosed during adolescence. At diagnosis, adolescent JSLE patients presented with a higher number of ACR criteria when compared with pre-pubertal and peri-pubertal patients pBILAG2004 scores: 9(4–20 vs. 7(3–13 vs. 7(3–14, respectively, p = 0.015 with increased activity in the following BILAG domains: mucocutaneous (p = 0.025), musculoskeletal (p = 0.029), renal (p = 0.027) and cardiorespiratory (p = 0.001). Furthermore, adolescent JSLE patients were more frequently ANA-positive (p = 0.034) and exhibited higher anti-dsDNA titres (p = 0.001). Pre-pubertal individuals less frequently presented with leukopenia (p = 0.002), thrombocytopenia (p = 0.004) or low complement (p = 0.002) when compared with other age groups. No differences were identified in disease activity (pBILAG2004 score), damage (SLICC damage index) and the number of ACR criteria fulfilled at last follow up.
Conclusions
Disease presentations and laboratory findings vary significantly between age groups within a national cohort of JSLE patients. Patients diagnosed during adolescence exhibit greater disease activity and “classic” autoantibody, immune cell and complement patterns when compared with younger patients. This supports the hypothesis that pathomechanisms may vary between patient age groups.
To achieve a consensus-based definition of Low Disease Activity (LDA) for use in cSLE trials.
The International cSLE T2T Task Force, comprising of paediatric rheumatologists/nephrologists, and adult ...rheumatologists undertook a series of Delphi surveys/consensus meetings to discuss, refine, and vote upon cSLE LDA criteria.
The Task Force agreed that LDA should be based upon the adult-SLE Lupus Low Disease Activity State definition (LLDAS), with modifications to make it applicable to cSLE (cLLDAS). They agreed upon five cLLDAS criteria: (1) SLE Disease Activity Index (SLEDAI)-2 K ≤4, with no activity in major organ systems; (2) no new features of lupus disease activity compared with the last assessment; (3) Physician Global Assessment score of ≤1 (0–3 scale); (4) prednisolone dose of ≤0.15 mg/kg/day, 7.5 mg/day/maximum; while on (5) stable antimalarials, immunosuppressives, and biologics.
A cSLE-appropriate definition of cLLDAS has been generated, maintaining alignment with the adult-SLE definition to promote life-course research.
•What is already known on this topic LLDAS has been extensively investigated in SLE, until now, a cSLE definition has been lacking.•What this study adds The cSLE T2T Task Force have derived a cSLE appropriate definition; childhood LLDAS.•How this study might affect research, practice or policy - The cLLDAS definition will facilitate the development of future T2T approaches.
Background
Juvenile-onset systemic lupus erythematosus (JSLE) is more severe than adult-onset disease, including more lupus nephritis (LN). Despite differences in phenotype/pathogenesis, treatment is ...based upon adult trials. This study aimed to compare treatment response, damage accrual, time to inactive LN and subsequent flare, in JSLE LN patients treated with mycophenolate mofetil (MMF) versus intravenous cyclophosphamide (IVCYC).
Methods
UK JSLE Cohort Study participants, ≤16 years at diagnosis, with ≥4 American College of Rheumatology criteria for SLE, with class III or IV LN, were eligible. Mann–Whitney U tests, Fisher's exact test and Chi-squared tests were utilized for statistical analysis.
Results
Of the patients, 34/51 (67%) received MMF, and 17/51 (33%) received IVCYC. No significant differences were identified at 4–8 and 10–14 months post-renal biopsy and last follow-up, in terms of renal British Isles Lupus Assessment Grade scores, urine albumin/creatinine ratio, serum creatinine, ESR, anti-dsDNA antibody, C3 levels and patient/physician global scores. Standardized Damage Index scores did not differ between groups at 13 months or at last follow-up. Inactive LN was attained 262 (141–390) days after MMF treatment, and 151 (117–305) days following IVCYC (p = 0.17). Time to renal flare was 451 (157–1266) days for MMF, and 343 (198–635) days for IVCYC (p = 0.47).
Conclusion
This is the largest study to date investigating induction treatments for proliferative LN in children, demonstrating comparability of MMF and IVCYC.
Objectives
The Systemic Lupus International Collaborating Clinics (SLICC) group proposed revised classification criteria for systemic lupus erythematosus (SLICC-2012 criteria). This study aimed to ...compare these criteria with the well-established American College of Rheumatology classification criteria (ACR-1997 criteria) in a national cohort of juvenile-onset systemic lupus erythematosus (JSLE) patients and evaluate how patients’ classification criteria evolved over time.
Methods
Data from patients in the UK JSLE Cohort Study with a senior clinician diagnosis of probable evolving, or definite JSLE, were analyzed. Patients were assessed using both classification criteria within 1 year of diagnosis and at latest follow up (following a minimum 12-month follow-up period).
Results
A total of 226 patients were included. The SLICC-2012 was more sensitive than ACR-1997 at diagnosis (92.9% versus 84.1% p < 0.001) and after follow up (100% versus 92.0% p < 0.001). Most patients meeting the SLICC-2012 criteria and not the ACR-1997 met more than one additional criterion on the SLICC-2012.
Conclusions
The SLICC-2012 was better able to classify patients with JSLE than the ACR-1997 and did so at an earlier stage in their disease course. SLICC-2012 should be considered for classification of JSLE patients in observational studies and clinical trial eligibility.
BackgroundRelapsing polychondritis (RP) in childhood is a rare multi-system disease characterised by inflammation of multiple cartilages. Progressive destruction of cartilaginous tissues in patients ...with tracheobronchial involvement can lead to life threatening exacerbations.Diagnosis in children and young people is often delayed due to rarity of this condition although the clinical course is often more severe than in adults with a higher incidence of laryngotracheobronchial involvement.Case ReportA 14-year-old of African descent presented to the children’s hospital with evidence of auricular inflammation, anterior rib pain and red, painful eyes. She had raised inflammatory markers and was treated with broad-spectrum antibiotics. RP was suspected and high dose oral steroids were commenced, improving all symptoms.On weaning steroids, she quickly relapsed and presented with upper airway problems including stridor, barking cough and increased work of breathing. Initial flexible nasendoscopy showed interarytenoid and subglottic oedema and likely tracheobronchitis. She was commenced on Rituximab and a six-month course of Cyclophosphamide.CT Neck and thorax showed focal obliteration of the airway at the level of hypopharynx and narrowing of left main bronchus. CT bronchogram showed the narrowing improved on a PEEP of 12 cm H2O. She was trialled on BiPAP overnight which helped her symptoms. She was referred to Great Ormond Street Hospital for a review; no further changes in management were suggested.The patient had recurrent relapses needing intensive care, therefore she was started on methotrexate and adalimumab, and had a balloon dilatation for her subglottic oedema and stenosis, which she tolerated well. She has been discharged home on overnight BiPAP with a plan for monthly balloon dilatations with ENT and to continue on methotrexate and adalimumab with gradual wean of steroids.ConclusionRP is rare with estimated incidence of 3.5 per million, only 10% cases are seen in paediatrics. Without aggressive and prompt treatment, life-threatening complications can develop rapidly, and outcomes are poor. Managing children with RP with significant airway involvement with NIV and repeated monthly balloon dilatations can help prevent life threatening exacerbations and the need for a tracheostomy. This case demonstrates the importance of multidisciplinary management of this complex condition.
Abstract
Objective
To evaluate the impact of anti-Tumour Necrosis Factor-α (anti-TNF) treatment on the occurrence of vasculitic ischaemic events in patients with deficiency of adenosine deaminase 2 ...(DADA2).
Methods
A retrospective analysis of DADA2 patients referred from six centres to Great Ormond Street Hospital for Children was conducted. Ischaemic events, vasculitic disease activity, biochemical, immunological, and radiological features were compared, before and after anti-TNF treatment.
Results
A total of 31 patients with genetically confirmed DADA2 were included in the study. The median duration of active disease activity prior to anti-TNF treatment was 73 months (inter-quartile range IQR 27.5–133.5 months). Twenty seven/31 patients received anti-TNF treatment for a median of 32 months (IQR 12.0–71.5 months). The median event rate of central nervous system (CNS) and non-CNS ischemic events before anti-TNF treatment was 2.37 per 100 patient-months (IQR 1.25–3.63); compared with 0.00 per 100 patient-months (IQR 0.0–0.0) post-treatment (p< 0.0001). Paediatric vasculitis activity score (PVAS) was also significantly reduced: median score of 20/63 (IQR 13.0–25.8/63) pre-treatment vs. 2/63 (IQR 0.0–3.8/63) following anti-TNF treatment (p< 0.0001), with mild livedoid rash being the main persisting feature. Anti-TNF treatment was not effective for severe immunodeficiency or bone marrow failure, which required haematopoietic stem cell transplantation (HSCT).
Conclusion
Anti-TNF treatment significantly reduced the incidence of ischaemic events and other vasculitic manifestations of DADA2, but was not effective for immunodeficiency or bone marrow failure.
Phase-contrast virtual chest radiography Häggmark, Ilian; Shaker, Kian; Nyrén, Sven ...
Proceedings of the National Academy of Sciences - PNAS,
01/2023, Letnik:
120, Številka:
1
Journal Article
Recenzirano
Odprti dostop
Respiratory X-ray imaging enhanced by phase contrast has shown improved airway visualization in animal models. Limitations in current X-ray technology have nevertheless hindered clinical translation, ...leaving the potential clinical impact an open question. Here, we explore phase-contrast chest radiography in a realistic in silico framework. Specifically, we use preprocessed virtual patients to generate in silico chest radiographs by Fresnel-diffraction simulations of X-ray wave propagation. Following a reader study conducted with clinical radiologists, we predict that phase-contrast edge enhancement will have a negligible impact on improving solitary pulmonary nodule detection (6 to 20 mm). However, edge enhancement of bronchial walls visualizes small airways (< 2 mm), which are invisible in conventional radiography. Our results show that phase-contrast chest radiography could play a future role in observing small-airway obstruction (e.g., relevant for asthma or early-stage chronic obstructive pulmonary disease), which cannot be directly visualized using current clinical methods, thereby motivating the experimental development needed for clinical translation. Finally, we discuss quantitative requirements on distances and X-ray source/detector specifications for clinical implementation of phase-contrast chest radiography.
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.
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