An Update on the Management of Childhood-Onset Systemic Lupus Erythematosus

Abstract

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.

Proportionate Cardiovascular Mortality in Chronic Inflammatory Disease in Adults in the United States From 1999 to 2019

“…Childhood-onset SLE is known to have an aggressive course with a higher rate of recurrence and complications, all of which can potentially contribute to the CVD and non-CVD mortality (including infections, active disease, etc). 26 The CVD proportionate mortality was significantly higher in patients with RA, SLE, and IBD at a younger age compared with the general population. Factors such as coronary microvascular dysfunction, dysregulation of the innate immune system, and chronic inflammation lead to accelerated atherosclerosis, arrhythmias, and cardiomyopathies, which all can contribute to early CVD mortality.…”

“…This may be partially explained given the high mortality due to childhood-onset of SLE. Childhood-onset SLE is known to have an aggressive course with a higher rate of recurrence and complications, all of which can potentially contribute to the CVD and non-CVD mortality (including infections, active disease, etc) 26 …”

Urine ALCAM, PF4 and VCAM-1 Surpass Conventional Metrics in Identifying Nephritis Disease Activity in Childhood-Onset Systemic Lupus Erythematosus

“…Childhood-onset systemic lupus erythematosus (cSLE) is a complex, chronic, multisystem autoimmune disease with a significant impact on the affected child or adolescent under 18 years of age. Despite sharing similar pathogenesis with adultonset SLE (aSLE), the clinical presentation of cSLE is generally more severe, with higher disease activity and damage, requiring more aggressive treatment (1)(2)(3)(4). cSLE comprises approximately 15-20% of SLE cases, with a prevalence of 1.89-25.7 per 100,000 children and an annual incidence of less than 1 per 100,000 children, rendering it a rare disease in childhood, with considerably lower rates than adults.…”

“…Compared to aSLE, cSLE exhibits higher frequencies of kidney, neuropsychiatric, and hematologic involvement (1,4). Lupus nephritis (LN) continues to be a prominent source of morbidity and mortality in SLE, reported in 30-40% of cSLE patients (3)(4)(5)(8)(9)(10)(11).…”

Diagnostic Delays and Psychosocial Outcomes of Childhood-Onset Systemic Lupus Erythematosus

“…Systemic lupus erythematosus (SLE) is a difficult-to-diagnose, chronic autoimmune disorder that involves multiple organs and manifests with a broad spectrum of clinical and immunological features [1,2]. Approximately 20% of patients with SLE present before 18 years of age and get diagnosed with childhoodonset systemic lupus erythematosus (cSLE) [3].…”