The road towards reducing damage in childhood SLE From clinics to blood vessels

This thesis focuses on childhood-onset systemic lupus erythematosus (cSLE), a rare systemic autoimmune disease. Despite improvements in treatment, preventing long-term disease-related damage remains challenging. The overall aim was to identify parameters that reflect or predict disease severity, potentially enabling early patient stratification and more personalised treatment strategies. Three main areas were investigated: nailfold capillaroscopy, disease-associated serum markers, and treat-to-target strategies.
First, nailfold capillaroscopy was evaluated as a non-invasive tool for assessing microvascular abnormalities. Different types of capillary haemorrhages could be reliably identified. A scleroderma capillary pattern was observed in a subgroup of patients and may be associated with an increased risk of organ damage. Furthermore, capillary density was influenced by skin pigmentation and ethnic background, factors that should be considered when interpreting capillaroscopic findings.
Second, disease-associated serum markers were investigated. Several markers related to endothelial activation were elevated at diagnosis. Some remained elevated despite low clinical disease activity, suggesting that vascular dysregulation may persist beyond the initial inflammatory phase and could contribute to long-term vascular complications.
Finally, the thesis examined a treat-to-target approach for cSLE and provided the first validation of the childhood Lupus Low Disease Activity State (cLLDAS). The findings highlight the importance of early glucocorticoid tapering and timely initiation of steroid-sparing therapies to reduce long-term damage.
Together, these findings provide important steps towards improved risk stratification and earlier, more personalised treatment of children with cSLE.