Management considerations for childhood-onset systemic lupus erythematosus patients and implications on therapy

ABSTRACT

Childhood-onset systemic lupus erythematosus (cSLE) is a chronic inflammatory and autoimmune disease that may involve various organs and systems. This narrative review focuses on the recent evidence relating to cSLE management. The general management considerations of cSLE patients require the use of validated classification criteria, disease and health-related quality of life tools evaluation, as well as assessments of lupus nephritis biomarkers and cSLE quality indicators. The drug treatment for cSLE patients includes general supportive care and immunosuppressive therapy. Important implications on cSLE therapy are also updated such as infection, vaccination, infertility, pregnancy, contraception, dyslipidemia, physical activity, cancer, bone health, drug pharmacokinetics, adherence, academic outcomes, transition to adult care and cumulative organ damage.

KEYWORDS:

• Childhood-onset systemic lupus erythematosus
• immunosuppressive
• infection
• vaccination
• dyslipidemia
• cancer
• vitamin D
• osteoporosis
• exercise
• fertility

Financial & competing interests disclosure

The authors are supported by grants from Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP 2014/14806-0 to CA Silva), Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 302724/2011-7 and 472155/2012-1 to CA Silva, and 301805/2013-0 to RMR Pereira), Federico Foundation (to CA Silva and RMR Pereira) and by Núcleo de Apoio à Pesquisa “Saúde da Criança e do Adolescente” da USP (NAP-CriAd) to CA Silva. The authors have no other relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript apart from those disclosed.

Key issues

• The new Systemic Lupus Collaborating Clinics classification criteria were validated for childhood-onset systemic lupus erythematosus (cSLE) populations, showing higher sensitivity and lower specificity than ACR criteria.

• Lupus nephritis biomarkers seem to be a useful tool to predict renal flares and to monitor the disease activity.

• Studies in cSLE populations generally were nonrandomized clinical trials and consensus/expert opinion, and the most important immunosuppressant drugs for cSLE treatment have never been tested for safety and efficacy in large populations.

• Hydroxychloroquine is indicated in all cSLE patients with or without nephritis. Prolonged use of glucocorticoid should be avoided in cSLE. Intravenous cyclophosphamide seems to have a better risk–benefit profile in cSLE compared to adults, mainly best adherence.

• cSLE patients had a higher susceptibility to herpes zoster infection but a lower frequency of postherpetic neuralgia than adult SLE. Invasive fungal infections occurred at early disease onset and with a high rate of fatal outcome.

• Intravenous cyclophosphamide therapy was the major factor in decreasing ovarian reserve and increasing sperm abnormalities in adolescents and young cSLE patients. Triptorelin for postpubertal females and sperm cryopreservation for future assisted reproductive technologies for postpubertal males should be started before or at the beginning of cyclophosphamide therapy.

• Atorvastatin may reduce atherosclerosis progression in postpubertal lupus patients with higher C-reactive protein.

• Aerobic exercise training was safe and capable of ameliorating the cardiorespiratory capacity and the autonomic function in cSLE patients.

• Vitamin D supplementation is indicated in cSLE patients with hypovitaminosis. A significant improvement of Systemic Lupus Erythematosus Disease Activity Index and fatigue related to social life score was observed in cholecalciferol-supplemented cSLE patients compared to controls.

• Inferior academic outcomes, low adherence and transition problems to adult care were evident in cSLE patients.