Sylvia Kamphuis - Academia.edu (original) (raw)

Papers by Sylvia Kamphuis

Arthritis & Rheumatism, Dec 12, 2002

Journal of the Pediatric Infectious Diseases Society, Dec 26, 2020

Background. In general, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection du... more Background. In general, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection during pregnancy is not considered to be an increased risk for severe maternal outcomes but has been associated with an increased risk for fetal distress. Maternal-fetal transmission of SARS-CoV-2 was initially deemed uncertain; however, recently a few cases of vertical transmission have been reported. The intrauterine mechanisms, besides direct vertical transmission, leading to the perinatal adverse outcomes are not well understood. Methods. Multiple maternal, placental, and neonatal swabs were collected for the detection of SARS-CoV-2 using real-time quantitative polymerase chain reaction (RT-qPCR). Serology of immunoglobulins against SARS-CoV-2 was tested in maternal, umbilical cord, and neonatal blood. Placental examination included immunohistochemical investigation against SARS-CoV-2 antigen expression, with SARS-CoV-2 ribonucleic acid (RNA) in situ hybridization and transmission electron microscopy. Results. RT-qPCRs of the oropharynx, maternal blood, vagina, placenta, and urine were all positive over a period of 6 days, while breast milk, feces, and all neonatal samples tested negative. Placental findings showed the presence of SARS-CoV-2 particles with generalized inflammation characterized by histiocytic intervillositis with diffuse perivillous fibrin depositions with damage to the syncytiotrophoblasts. Conclusions. Placental infection by SARS-CoV-2 leads to fibrin depositions hampering fetal-maternal gas exchange with resulting fetal distress necessitating a premature emergency cesarean section. Postpartum, the neonate showed a fetal or pediatric inflammatory multisystem-like syndrome with coronary artery ectasia temporarily associated with SARS-CoV-2 for which admittance and care on the neonatal intensive care unit (NICU) were required, despite being negative for SARS-CoV-2. This highlights the need for awareness of adverse fetal and neonatal outcomes during the current coronavirus disease 2019 pandemic, especially considering that the majority of pregnant women appear asymptomatic.

Rheumatology International, Apr 1, 2018

The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reporte... more The Juvenile Arthritis Multidimensional Assessment Report (JAMAR) is a new parent/patient reported outcome measure that enables a thorough assessment of the disease status in children with juvenile idiopathic arthritis (JIA). We report the results of the cross-cultural adaptation and validation of the parent and patient versions of the JAMAR in the Dutch language. The reading comprehension of the questionnaire was tested in ten JIA parents and patients. Each participating centre was asked to collect demographic, clinical data and the JAMAR in 100 consecutive JIA patients or all consecutive patients seen in a 6-month period and to administer the JAMAR to 100 healthy children and their parents. The statistical validation phase explored descriptive statistics and the psychometric issues of the JAMAR: the three Likert assumptions, floor/ceiling effects, internal consistency, Cronbach's alpha, interscale correlations, test-retest reliability, and construct validity (convergent and discriminant validity). A total of 209 JIA patients (14.3% systemic, 39.7% oligoarticular, 25.8% RF negative polyarthritis, 20.2% other categories) and 107 healthy children were enrolled in two centres. The JAMAR components discriminated well healthy subjects from JIA patients. All JAMAR components revealed good psychometric performances. In conclusion, the Dutch version of the JAMAR is a valid tool for the assessment of children with JIA and is suitable for use both in routine clinical practice and clinical research.

Pediatric Rheumatology, Sep 1, 2014

Lupus science & medicine, Feb 1, 2022

Nassar-Sheikh Rashid A, et al. Nailfold capillary scleroderma pattern may be associated with dise... more Nassar-Sheikh Rashid A, et al. Nailfold capillary scleroderma pattern may be associated with disease damage in childhood-onset systemic lupus erythematosus: important lessons from longitudinal followup.

Arthritis Research & Therapy, Dec 1, 2018

Background: The availability of methotrexate and the introduction of multiple biological agents h... more Background: The availability of methotrexate and the introduction of multiple biological agents have revolutionized the treatment of juvenile idiopathic arthritis (JIA). Several international and national drug registries have been implemented to accurately monitor the long-term safety/efficacy of these agents. This report aims to present the combined data coming from Pharmachild/PRINTO registry and the national registries from Germany (BiKeR) and Sweden. Methods: Descriptive statistics was used for demographic, clinical data, drug exposure, adverse events (AEs) and events of special interest (ESIs). For the Swedish register, AE data were not available. Results: Data from a total of 15,284 patients were reported: 8274 (54%) from the Pharmachild registry and 3990 (26%) and 3020 (20%) from the German and the Swedish registries, respectively. Pharmachild children showed a younger age (median of 5.4 versus 7.6 years) at JIA onset and shorter disease duration at last available visit (5.3 versus 6.1-6.8) when compared with the other registries. The most frequent JIA category was the rheumatoid factor-negative polyarthritis (range of 24.6-29.9%). Methotrexate (61-84%) and etanercept (24%-61.8%) were the most frequently used synthetic and biologic disease-modifying anti-rheumatic drugs (DMARDs), respectively. There was a wide variability in glucocorticoid use (16.7-42.1%). Serious AEs were present in 572 (6.9%) patients in Pharmachild versus 297 (7.4%) in BiKeR. Infection and infestations were the most frequent AEs (29.4-30.1%) followed by gastrointestinal disorders (11.5-19.6%). The most frequent ESIs were infections (75.3-89%).

Annals of the Rheumatic Diseases, Sep 6, 2017

Background Lupus nephritis (LN) occurs in 50-60% of patients with childhood-onset systemic lupus ... more Background Lupus nephritis (LN) occurs in 50-60% of patients with childhood-onset systemic lupus erythematosus (cSLE), leading to significant morbidity. Timely recognition of renal involvement and appropriate treatment are essential to prevent renal damage. Objectives To provide evidence-based recommendations for diagnosis and treatment of LN in childhood. Methods The SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) initiative was launched in 2012 to generate diagnostic and management regimens for children and adolescents with rheumatic diseases such as cSLE. Recommendations were developed using the European League Against Rheumatism (EULAR) standard operating procedure. A European-wide expert committee including representation of paediatric nephrology formulated recommendations using the nominal group technique. Results Six recommendations regarding diagnosis and twenty recommendations covering treatment choices and goals were accepted for the different classes of LN, described in the International Society of Nephrology/Renal Pathology Society (ISN/RPS) 2003 classification system. Treatment goal should be complete renal response. Treatment of class I LN should mainly be guided by other symptoms. Class II LN should be treated initially with low-dose prednisone, only adding a DMARD after 3 months of persistent proteinuria or prednisone dependency. Induction treatment of class III/IV LN should be mycophenolate mofetil (MMF) or intravenous cyclophosphamide combined with corticosteroids; maintenance treatment should be MMF or azathioprine for at least 3 years. In pure class V LN, MMF with low-dose prednisone can be used as induction and MMF as maintenance treatment. Conclusions Evidence-based recommendations for diagnosis and treatment of LN have been generated to support uniform and high quality care for all children with SLE.

Annals of the Rheumatic Diseases, Jun 19, 2017

Background Childhood-onset systemic lupus erythematosus (cSLE) is a rare, multisystem autoimmune ... more Background Childhood-onset systemic lupus erythematosus (cSLE) is a rare, multisystem autoimmune disorder with significant associated morbidity. Evidence-based guidelines are sparse and management is often based on a clinician's previous experience. In 2012, a European initiative called SHARE (Single Hub and Access point for paediatric Rheumatology in Europe) was launched to optimize and disseminate diagnostic and management regimens in Europe for children and young adults with rheumatic diseases such as cSLE. Objectives To provide evidence-based recommendations for diagnosis and treatment of cSLE including neuro-psychiatric lupus. Methods Recommendations were generated using the European League Against Rheumatism (EULAR) standard operating procedure. An expert committee, consisting of paediatric rheumatologists from across Europe discussed evidence based recommendations during two consensus meetings using a nominal group technique. Recommendations were accepted if >80% agreement was reached. Results A total of twenty-five recommendations were made tackling key approaches to the diagnosis and treatment of cSLE including: eleven for diagnosis, nine on disease monitoring, and five on general treatment. Topics included: appropriate use of SLE classification criteria, disease activity and damage indices; careful assessment of autoantibody profiles; low threshold of suspicion for secondary macrophage activation syndrome; use of hydroxychloroquine and corticosteroid sparing regimens; and the importance of addressing poor adherence. An additional ten recommendations were agreed regarding general diagnostic strategies and treatment indications of neuropsychiatric cSLE. Conclusions The SHARE recommendations for cSLE and neuropsychiatric manifestations of cSLE have been formulated by an evidence-informed consensus process to support uniform, high quality standards of care for children with cSLE throughout Europe.

Rheumatology, Mar 16, 2019

is the commonest cause of systemic vasculitis in childhood. 2. These are the first international,... more is the commonest cause of systemic vasculitis in childhood. 2. These are the first international, evidence-based recommendations concerning the management of childhood IgA Vasculitis. 3. All IgA Vasculitis patients need proactively investigated for renal involvement, at diagnosis and throughout follow-up.

Pediatric Clinics of North America, Apr 1, 2012

Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that can involve any organ sys... more Systemic Lupus Erythematosus (SLE) is a chronic autoimmune disease that can involve any organ system with a wide range of disease manifestations, and can lead to significant morbidity and even mortality. This article reviews the epidemiology, common clinical features, complications of disease, and briefly discusses the available treatment options. In addition, important medical and psychosocial issues relevant to the pediatrician caring for children and adolescents with SLE are discussed.

Journal of Inflammation, May 16, 2023

Objectives To perform a systematic literature review and meta-analysis on endothelial cell (EC) m... more Objectives To perform a systematic literature review and meta-analysis on endothelial cell (EC) markers that are involved and dysregulated in systemic lupus erythematosus (SLE) in relation to disease activity, as EC dysregulation plays a major role in the development of premature atherosclerosis in SLE. Methods Search terms were entered into Embase, MEDLINE, Web of Science, Google Scholar and Cochrane. Inclusion criteria were 1) studies published after 2000 reporting measurements of EC markers in serum and/or plasma of SLE patients (diagnosed according to ACR/SLICC criteria), 2) English language peer reviewed articles, and 3) disease activity measurement. For meta-analysis calculations, the Meta-Essentials tool by Erasmus Research Institute and of Management (ERIM) was used. Only those EC markers, which were 1) reported in at least two articles and 2) reported a correlation coefficient (i.e. Spearman's rank or Pearson's) between the measured levels of the EC marker and disease activity were included. For meta-analyses, a fixed effect model was used. Results From 2133 hits, 123 eligible articles were selected. The identified SLE-related endothelial markers were involved in EC activation, EC apoptosis, disturbed angiogenesis, defective vascular tone control, immune dysregulation and coagulopathy. Meta-analyses of primarily cross-sectional studies showed significant associations between marker levels and disease activity for the following endothelial markers: Pentraxin-3, Thrombomodulin, VEGF, VCAM-1, ICAM-1, IP-10 and MCP-1. Dysregulated EC markers without associations with disease activity were: Angiopoeitin-2, vWF, P-Selectin, TWEAK and E-Selectin. Conclusions We provide a complete literature overview for dysregulated EC markers in SLE comprising a wide range of different EC functions. SLE-induced EC marker dysregulation was seen with, but also without, association with disease activity. This study provides some clarity in the eminent complex field of EC markers as biomarkers for SLE. Longitudinal data on EC markers in SLE are now needed to guide us more in unravelling the pathophysiology of premature atherosclerosis and cardiovascular events in SLE patients.

Rheumatology, Dec 14, 2022

Objective: To study the association of serum IFNa2 levels measured by ultrasensitive single-molec... more Objective: To study the association of serum IFNa2 levels measured by ultrasensitive single-molecule array (Simoa) and the IFN-I gene signature (IGS) with disease activity and determine whether these assays can mark disease activity states in a longitudinal cohort of childhood-onset SLE (cSLE) patients. Methods: Serum IFNa2 levels were measured in 338 samples from 48 cSLE patients and 67 healthy controls using an IFNa Simoa assay. Five-gene IGS was measured by RT-PCR in paired whole blood samples. Disease activity was measured by clinical SELENA-SLEDAI and BILAG-2004. Low disease activity was defined by Low Lupus Disease Activity State (LLDAS) and flares were characterized by SELENA-SLEDAI flare index. Analysis was performed using linear mixed models. Results: A clear positive correlation was present between serum IFNa2 levels and the IGS (r ¼ 0.78, P < 0.0001). Serum IFNa2 levels and IGS showed the same significant negative trend in the first 3 years after diagnosis. In this timeframe, mean baseline serum IFNa2 levels decreased by 55.1% (D 201 fg/ml, P < 0.001) to a mean value of 164 fg/ml, which was below the calculated threshold of 219.4 fg/ml that discriminated between patients and healthy controls. In the linear mixed model, serum IFNa2 levels were significantly associated with both cSELENA-SLEDAI and BILAG-2004, while the IGS did not show this association. Both IFN-I assays were able to characterize LLDAS and disease flare in receiver operating characteristic analysis. Conclusions: Serum IFNa2 levels measured by Simoa technology are associated with disease activity scores and characterize disease activity states in cSLE.

Frontiers in Immunology, Jul 4, 2022

Background: Trained immunityor innate immune memorycan be described as the long-term reprogrammin... more Background: Trained immunityor innate immune memorycan be described as the long-term reprogramming of innate immune cells towards a hyperresponsive state which involves intracellular metabolic changes. Trained immunity has been linked to atherosclerosis. A subgroup of patients with primary Sjögren's syndrome (pSS) exhibits systemic type I interferon (IFN) pathway activation, indicating innate immune hyperactivation. Here, we studied the link between type I IFNs and trained immunity in an in vitro monocytic cell model and peripheral blood mononuclear cells (PBMCs) from pSS patients. Methods: The training stimuli heat killed Candida albicans, muramyl dipeptide, IFNb, and patient serum were added to THP-1 cells for 24 hours, after which the cells were washed, rested for 48 hours and subsequently re-stimulated with LPS, Pam3Cys, poly I:C, IFNb or oxLDL for 4-24 hours. PBMCs from pSS patients and healthy controls were stimulated with LPS, Pam3Cys, poly I:C or IFNb for 0.5-24 hours. Results: Training with IFNb induced elevated production of pro-atherogenic cytokines IL-6, TNFa and CCL2, differential cholesterol-and glycolysis-related gene expression, and increased glucose consumption and oxLDL uptake upon re-stimulation. Type I IFN production was increased in Candida albicans-and IFNb-trained cells after LPS restimulation, but was reduced after poly I:C re-stimulation. Training with muramyl dipeptide

Rheumatology, Feb 10, 2022

Objectives. Clinical phenotyping and predicting treatment responses in SLE patients is challengin... more Objectives. Clinical phenotyping and predicting treatment responses in SLE patients is challenging. Extensive blood transcriptional profiling has identified various gene modules that are promising for stratification of SLE patients. We aimed to translate existing transcriptomic data into simpler gene signatures suitable for daily clinical practice. Methods. Real-time PCR of multiple genes from the IFN M1.2, IFN M5.12, neutrophil (NPh) and plasma cell (PLC) modules, followed by a principle component analysis, was used to identify indicator genes per gene signature. Gene signatures were measured in longitudinal samples from two childhood-onset SLE cohorts (n ¼ 101 and n ¼ 34, respectively), and associations with clinical features were assessed. Disease activity was measured using Safety of Estrogen in Lupus National Assessment (SELENA)-SLEDAI. Cluster analysis subdivided patients into three mutually exclusive fingerprint-groups termed (1) all-signatures-low, (2) only IFN high (M1.2 and/or M5.12) and (3) high NPh and/or PLC. Results. All gene signatures were significantly associated with disease activity in cross-sectionally collected samples. The PLC-signature showed the highest association with disease activity. Interestingly, in longitudinally collected samples, the PLC-signature was associated with disease activity and showed a decrease over time. When patients were divided into fingerprints, the highest disease activity was observed in the high NPh and/or PLC group. The lowest disease activity was observed in the all-signatures-low group. The same distribution was reproduced in samples from an independent SLE cohort. Conclusions. The identified gene signatures were associated with disease activity and were indicated to be suitable tools for stratifying SLE patients into groups with similar activated immune pathways that may guide future treatment choices.

Lupus science & medicine, Dec 1, 2021

Objectives To study whether clinical remission (CR) and Low Lupus Disease Activity State (LLDAS) ... more Objectives To study whether clinical remission (CR) and Low Lupus Disease Activity State (LLDAS) are achievable goals in childhood-onset SLE. Methods Data on medication use and disease activity were prospectively collected. LLDAS was defined as Safety of Estrogen in Lupus Erythematosus National Assesment-SLE disease Activity Index (SELENA-SLEDAI) ≤4 with zero scores for renal, Central Nervous System (CNS), serositis, vasculitis and constitutional components, no increase in any SLEDAI component since the previous visit, PGA ≤1, and prednisone dose ≤7.5 mg/day. CR on treatment (Tx) was defined as a Physician Global Assessment <0.5, SELENA-SLEDAI=0, with prednisone ≤5 mg/day and maintenance treatment with immunosuppressives. CR off Tx was the same but without prednisone or other immunosuppressive usage. Results 51 patients (700 visits) were included. Within 3 months after diagnosis, 94.1% of children were treated with hydroxychloroquine and 60.8% with prednisone. Prednisone dosage decreased from a median of 0.74 mg/ kg/day at diagnosis to 0.44 mg/kg/day at 3 months and 0.16 mg/kg/day at 6 months after diagnosis. Use of mycophenolate mofetil increased from 25.5% to 56.9% within 6 months after diagnosis. All children achieved LLDAS (median 186 days) and 72.5% remained in LLDAS >50% of time. 52.9% children achieved CR on Tx, and only 21.6% children achieved CR off Tx. Conclusions LLDAS is an attainable treat-to-target goal in contrast to CR on and off Tx. Even more, LLDAS can be reached with limited use of corticosteroids with early introduction of immunosuppressives.

Annals of the Rheumatic Diseases, Jul 23, 2014

Juvenile idiopathic arthritis (JIA) is considered a complex genetic autoimmune disease. We invest... more Juvenile idiopathic arthritis (JIA) is considered a complex genetic autoimmune disease. We investigated the association of genetic variants previously implicated in JIA, autoimmunity and/or immunoregulation, with susceptibility to JIA. A genetic association study was performed in 639 JIA patients and 1613 healthy controls of northwest European descent. Ninety-three single nucleotide polymorphisms (SNP) were genotyped in a candidate gene approach. Results of the entire JIA patient group (all subtypes) were compared with results obtained, alternatively, with a clinically homogeneous patient group including only oligoarticular and rheumatoid factor (RF) negative polyarticular JIA patients (n=493). Meta-analyses were performed for all SNPs that have been typed in other Caucasian JIA cohorts before. SNPs in or near PTPN22, VTCN1, the IL2-IL21 region, ANKRD55 and TNFA were confirmed to be associated with JIA (p&amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;amp;lt;0.05), strengthening the evidence for involvement of these genes in JIA. In the majority of these replicated SNPs, effect sizes were larger when analysing a homogeneous patient cohort than when analysing all subtypes. We identified two novel associations with oligoarticular and RF-negative polyarticular JIA: CD226 rs763361 (OR 1.30, 95% CI 1.12 to 1.51, p=0.0006) and CD28 rs1980422 (OR 1.29, 95% CI 1.07 to 1.55, p=0.008). Meta-analyses including reported studies confirmed the association of both SNPs with susceptibility to JIA (OR 1.16, p=0.001 and OR 1.18, p=0.001, for rs763361 and rs1980422, respectively). The CD226 gene has been identified as novel association with JIA, and a SNP near CD28 as a suggestive association. Both genes are probable candidate risk factors, since they are involved in costimulation of T cells.

Pediatric Rheumatology, Aug 3, 2018

Background: In 2008 a clinical transition pathway for young people with juvenile-onset rheumatic ... more Background: In 2008 a clinical transition pathway for young people with juvenile-onset rheumatic and musculoskeletal diseases (jRMD) aiming at improving transitional care was instituted. Historical data on drop-out rate in our clinic was 35%, one year before the implementation of the transition pathway. This study aims to I) evaluate the effectiveness of the clinical transition pathway, II) evaluate the experiences and satisfaction of YP with the transitional process and evaluate their perceived self-management skills. Methods: Young people with any jRMD transferred from the pediatric to the adult rheumatology department in our academic center were eligible to enroll in this quantitative cross-sectional observational study between 2009 and 2015. Notably in 2012, we created a dedicated adolescent JIA-clinic, located at the adult rheumatology department. Electronic patient records from all young people that were transferred between 2009 and 2015 were reviewed for drop-out of care. Young people were asked to rate a VAS for 'satisfaction with transition' and to complete the "on your own feet transfer experience scale" (OYOF-TES)-questionnaire regarding their experiences and satisfaction with transition. Self-management skills were measured with the "on your own feet self-efficacy scale" (OYOF-SES)-questionnaire. Results: One hundred fifty-four young people were transferred to the adult department, of which 76 were transferred to the dedicated adolescent JIA-clinic. The mean age at transfer was 17.8 years for YP transferred to the adult clinic and 15.2 years for transfer to the adolescent clinic. Drop-out of care rate one year after transfer was 5. 1% in the adult clinic and 1.3% in the adolescent JIA-clinic. Response rate of the returned questionnaires was 61% for the adolescent JIA clinic and 36% for the adult clinic. There was no difference between responders and nonresponders in demographics and disease type besides age (non-responders were significantly younger). Young people transferred to the adult and adolescent JIA-clinic both had high scores on the satisfaction scale (7.7 and 7.5 on the VAS-scale and 72.0 and 74.5 on the OYOF-TES). Self-efficacy scores were high for both groups, with OYOF-SES 59.7 for those transferred to the adult clinic and 58.2 for those transferred to the adolescent JIA-clinic. Conclusion: The implementation of the clinical transition pathway has led to a substantial improvement of patient care during the transitional process leading to low drop-out of care rate and high scores on satisfaction with transition. High scores on the self-reported self-efficacy scale suggests confidence of young people to have achieved sufficient skills to successfully manage their disease.

Annals of the Rheumatic Diseases

BackgroundIn (childhood-onset) systemic lupus erythematosus ((c)SLE), patients have an increased ... more BackgroundIn (childhood-onset) systemic lupus erythematosus ((c)SLE), patients have an increased risk of developing premature atherosclerosis [1]. The pathophysiological mechanisms for this atherosclerosis are not completely understood. Besides traditional risk factors, the endothelium plays a major role [2]. Dysregulated endothelial cell markers and proteins involved in endothelial function in SLE are not always correlated to disease activity, which could mean that the endothelium stays in a dysregulated state in SLE, even with low disease activity (Bergkamp et al., submitted). However, previous studies were mostly cross-sectional and only performed in adult SLE, while childhood-onset SLE (cSLE) has a longer and more severe course [3,4].ObjectivesTo measure the serum levels of a panel of SLE-associated markers involved in endothelial cell (EC) function, in longitudinal samples of cSLE patients (active vs. low SLE disease activity index (SLEDAI)) and to compare them with healthy con...