Childhood-onset systemic lupus erythematosus (cSLE) is a prototype of a 
multisystemic, inflammatory, heterogeneous autoimmune condition. This disease is 
characterized by simultaneous or sequential organ and system involvement, with 
unpredictable flare and high levels of morbidity and mortality. Racial/ethnic 
background, socioeconomic status, cost of medications, difficulty accessing 
health care, and poor adherence seem to impact lupus outcomes and treatment 
response. In this article, the management of cSLE patients is updated. Regarding 
pathogenesis, a number of potential targets for drugs have been studied. 
However, most treatments in pediatric patients are off-label drugs with 
recommendations based on inadequately powered studies, therapeutic consensus 
guidelines, or case series. Management practices for cSLE patients include 
evaluations of disease activity and cumulative damage scores, routine non-live 
vaccinations, physical activity, and addressing mental health issues. 
Antimalarials and glucocorticoids are still the most common drugs used to treat 
cSLE, and hydroxychloroquine is recommended for nearly all cSLE patients. 
Disease-modifying antirheumatic drugs (DMARDs) should be standardized for each 
patient, based on disease flare and cSLE severity. Mycophenolate mofetil or 
intravenous cyclophosphamide is suggested as induction therapy for lupus 
nephritis classes III and IV. Calcineurin inhibitors (cyclosporine, tacrolimus, 
voclosporin) appear to be another good option for cSLE patients with lupus 
nephritis. Regarding B-cell-targeting biologic agents, rituximab may be used for 
refractory lupus nephritis patients in combination with another DMARD, and 
belimumab was recently approved by the US Food and Drug Administration for cSLE 
treatment in children aged > 5 years. New therapies targeting CD20, such as 
atacicept and telitacicept, seem to be promising drugs for SLE patients. 
Anti-interferon therapies (sifalimumab and anifrolumab) have shown beneficial 
results in phase II randomized control trials in adult SLE patients, as have 
some Janus kinase inhibitors, and these could be alternative treatments for 
pediatric patients with severe interferon-mediated inflammatory disease in the 
future. In addition, strict control of proteinuria and blood pressure is 
required in cSLE, especially with angiotensin-converting enzyme inhibitor and 
angiotensin receptor blocker use.