Childhood Lupus cohort study

Systemic Lupus Erythematosus (SLE) is a chronic auto-immune disease with a
highly heterogeneous presentation that may involve almost any organ system.
Disease onset during childhood occurs in 10 - 20% of SLE patients. Childhood
onset SLE (cSLE) follows a more aggressive course: disease activity is higher
both at onset and during life. Immunosuppressive medication is used in order to
manage the disease. However, despite aggressive drug regimes, cumulative damage
over time is higher and develops faster in these patients, and drug-free
remission is rarely achieved. Additionally, quality of life in cSLE patients is
gravely influenced by the effects of the disease and medication.

cSLE is a rare disease (incidence 0.3 - 0.9, prevalence of 3.3 - 8.8 per
100.000 children), which means that medical specialists do not see these
patients often. Standards of care and treatment guidelines are lacking, which
leads to differences in management and quality of care.

Nationally combining knowledge on the clinical presentation, management and
possible prognostic factors of cSLE in the Netherlands and analyzing the impact
of the disease on quality of life and other related issues will help to improve
care in the future.

In addition the care for SLE patients with involvement of the nervous system
has to be improved. We call this neuro-psychiatric SLE (NP-SLE). This is the
most severe presentation of SLE and more common in children than in adults. In
NP-SLE, the brain or peripheral nervous system are involved, leading to
symptoms like (severe) headaches, impaired cognitive functioning, epilepsy,
hallucinations and brain infarctions. Unfortunately, the diagnosis of NP-SLE in
children is difficult to make because symptoms are non-specific and current
diagnostic tools are not accurate enough. Unfortunately, patients and doctors
are left in doubt about the correct diagnosis leading to (unintended)
inadequate treatment. This has great clinical implications because NP-SLE
patients have a more severe course of the disease, develop more damage and die
more often than non-NP-SLE patients. Therefore, better recognition of NP-SLE is
essential to improve the outcome of these severely ill children.

To initiate a Dutch cohort with standardized follow-up measures and
investigating blood, liquor, urine samples and videocapillaroscopy findings
(nailfold and under the tongue) for prognostic factors during disease
quiescence and at times of disease flare. This will provide valuable insights
in the clinical presentation, disease outcome and will lead to the development
of new biomarkers.

In addition, the aim of this project is to find new diagnostic tools to improve
diagnosing children with NP-SLE.
The objectives for this are:
1. better identification of clinical symptomatology of NP-SLE using structured
and detailed analysis of patient histories and physical
examination, neuropsychological testing and detailed questionnaires for
patients on clinical neuropsychiatric symptoms;
2. using innovative Brain MR-Imaging techniques to detect NP-SLE;
3. using new electrophysiological brain testing to identify brain networks and
patterns characteristic of NP-SLE;
4. detecting novel and existing neuronal surface auto-antibodies in both serum
and cerebrospinal fluid by using immunohistochemistry
techniques, immunocytochemistry (live hippocampal neurons) and existing or
newly developed cell-based assays;
5. developing a diagnostic algorithm for the diagnosis of NP-SLE and form this
into an evidence-based diagnostic guideline that can
easily be used in clinical practice.

Multicentre longitudinal observational cohort study

Principally, all investigations and procedures listed in the study protocol and
intended to be executed and collected in our study patients, are part of normal
clinical practice and considered *standard of care*. These procedures hence do
not oppose an increased risk or burden for included patients. Only with respect
to health analysis we aim to collect data from short validated questionnaires
not directly related to standard care of our patients (i.e. quality of life and
fatigue). Standard of care laboratory examinations are carried out at each
visit. In addition, for a maximum of 6 times/year, and only if routine care
laboratory investigations are already warranted, a limited amount of extra
blood and, if applicable, urine samples will be collected for research
intentions. The frequency of sampling, the total volume per sampling time and
the total cumulative volume sampled per year will remain well within the limits
of the WHO guidelines on peripheral blood sampling for minors of 2015 (~0,8
ml/kg/sampling time with a maximum of 50 ml/draw, not exceeding 6 times a year).

If a lumbar puncture is performed for diagnostic purposes an extra amount of
liquor (maximum of 3ml) will be collected for the study.

Videocapillaroscopy of the blood vessels in the nailfold and under the tongue
is a non-invasive, non-painful method to visualize the smallest blood vessels
in the nailfold area of the fingertips and under the tongue. These procedures
are painless and do not cause any harm to the patient.

For the NP-SLE part of the study, patients will visit the Sophia Children's
hospital once for a study visit, MRI and EEG. Performing those investigations
does not oppose any health risk or burden, but some patients may find it time
consuming (on average, 4 hours). The travel and lunch costs will be compensated.

The risks associated with participation in this study for our patients are
estimated to be negligible and the burden minimal. There are no direct benefits
for the participants. There is a group benefit for future patients with cSLE.