Diagnosis and Management of Pediatric Neuropsychiatric Systemic Lupus Erythematosus: An Update

Overview

Journal Paediatr Drugs

Specialties Pediatrics
Pharmacology

Date 2024 May 28

PMID 38805115

Authors

Dilara Unal

Veysel Cam

Hulya Ercan Emreol

Seza Ozen

Affiliations

Soon will be listed here.

Abstract

Neuropsychiatric systemic lupus erythematosus (NPSLE) is a potentially serious and life-threatening complication of SLE. The presentation and severity of neuropsychiatric involvement in SLE may show considerable variability. The disease can affect the neural tissue directly or may be associated with vascular involvement, mainly associated with anti-phospholipid (aPL) antibodies. A direct causal link with SLE may sometimes be challenging since there are many confounding factors and the symptoms may be non-specific. Despite its remarkable sensitivity in detecting hemorrhagic and ischemic stroke, transverse myelitis and ischemic infarction, magnetic resonance imaging (MRI) lacks the spatial resolution required to identify microvascular involvement. When standard MRI fails to detect a suspicious lesion, it is advisable to use advanced imaging modalities such as positron emission tomography (PET), single photon emission computed tomography (SPECT) or quantitative MRI, if available. Even with these advanced modalities, the specificity of neuroimaging in NPSLE remains inadequate (60-82% for MRI). Neuropsychiatric syndromes, such as cerebrovascular events, seizures and cognitive impairments appear to be associated with serum aPL antibodies. Some studies have shown that anti-ribosomal P antibodies have a low sensitivity for NPSLE and a limited contribution to the differentiation of different clinical entities. Treatment has two main goals: symptomatic relief and treatment of the disease itself. Commonly used immunosuppressants for NPSLE include cyclophosphamide (CYC), azathioprine (AZA), and mycophenolate mofetil (MMF). According to EULAR's current recommendation, strong immunosuppressants such as CYC and rituximab (RTX) should be preferred. Biologics have also been used in NPSLE. Fingolimod, eculizumab, and JAK inhibitors are potential drugs in the pipeline. Developing targeted therapies will be possible by a better understanding of the pathological mechanisms.

References

Smith E, Lythgoe H, Midgley A, Beresford M, Hedrich C . Juvenile-onset systemic lupus erythematosus: Update on clinical presentation, pathophysiology and treatment options. Clin Immunol. 2019; 209:108274. DOI: 10.1016/j.clim.2019.108274. View

Silva C, Avcin T, Brunner H . Taxonomy for systemic lupus erythematosus with onset before adulthood. Arthritis Care Res (Hoboken). 2012; 64(12):1787-93. PMC: 3463746. DOI: 10.1002/acr.21757. View

Hedrich C, Smith E, Beresford M . Juvenile-onset systemic lupus erythematosus (jSLE) - Pathophysiological concepts and treatment options. Best Pract Res Clin Rheumatol. 2018; 31(4):488-504. DOI: 10.1016/j.berh.2018.02.001. View

Rees F, Doherty M, Grainge M, Davenport G, Lanyon P, Zhang W . The incidence and prevalence of systemic lupus erythematosus in the UK, 1999-2012. Ann Rheum Dis. 2014; 75(1):136-41. PMC: 4717400. DOI: 10.1136/annrheumdis-2014-206334. View

Muscal E, Brey R . Neurologic manifestations of systemic lupus erythematosus in children and adults. Neurol Clin. 2009; 28(1):61-73. PMC: 2981505. DOI: 10.1016/j.ncl.2009.09.004. View

Giani T, Smith E, Al-Abadi E, Armon K, Bailey K, Ciurtin C . Neuropsychiatric involvement in juvenile-onset systemic lupus erythematosus: Data from the UK Juvenile-onset systemic lupus erythematosus cohort study. Lupus. 2021; 30(12):1955-1965. PMC: 8649437. DOI: 10.1177/09612033211045050. View

Unterman A, Nolte J, Boaz M, Abady M, Shoenfeld Y, Zandman-Goddard G . Neuropsychiatric syndromes in systemic lupus erythematosus: a meta-analysis. Semin Arthritis Rheum. 2010; 41(1):1-11. DOI: 10.1016/j.semarthrit.2010.08.001. View

Baisya R, Devarasetti P, Narayanan R, Rajasekhar L . Posterior reversible encephalopathy syndrome in juvenile lupus- a case series and literature review. Lupus. 2022; 31(5):606-612. DOI: 10.1177/09612033221088207. View

10.

Vina E, Fang A, Wallace D, Weisman M . Chronic inflammatory demyelinating polyneuropathy in patients with systemic lupus erythematosus: prognosis and outcome. Semin Arthritis Rheum. 2005; 35(3):175-84. DOI: 10.1016/j.semarthrit.2005.08.008. View

11.

Singh S, Gupta M, Ahluwalia J, Singh P, Malhi P . Neuropsychiatric manifestations and antiphospholipid antibodies in pediatric onset lupus: 14 years of experience from a tertiary center of North India. Rheumatol Int. 2009; 29(12):1455-61. DOI: 10.1007/s00296-009-0887-6. View

12.

Ambrose N, Morgan T, Galloway J, Ionnoau Y, Beresford M, Isenberg D . Differences in disease phenotype and severity in SLE across age groups. Lupus. 2016; 25(14):1542-1550. PMC: 5089221. DOI: 10.1177/0961203316644333. View

13.

Amaral B, Murphy G, Ioannou Y, Isenberg D . A comparison of the outcome of adolescent and adult-onset systemic lupus erythematosus. Rheumatology (Oxford). 2014; 53(6):1130-5. DOI: 10.1093/rheumatology/ket488. View

14.

Choi J, Park D, Kang J, Yim Y, Lee K, Lee J . Comparison of clinical and serological differences among juvenile-, adult-, and late-onset systemic lupus erythematosus in Korean patients. Lupus. 2015; 24(12):1342-9. DOI: 10.1177/0961203315591024. View

15.

Govoni M, Hanly J . The management of neuropsychiatric lupus in the 21st century: still so many unmet needs?. Rheumatology (Oxford). 2020; 59(Suppl5):v52-v62. PMC: 7719041. DOI: 10.1093/rheumatology/keaa404. View

16.

Hanly J, Mccurdy G, Fougere L, Douglas J, Thompson K . Neuropsychiatric events in systemic lupus erythematosus: attribution and clinical significance. J Rheumatol. 2004; 31(11):2156-62. View

17.

Tucker L, Uribe A, Fernandez M, Vila L, McGwin G, Apte M . Adolescent onset of lupus results in more aggressive disease and worse outcomes: results of a nested matched case-control study within LUMINA, a multiethnic US cohort (LUMINA LVII). Lupus. 2008; 17(4):314-22. PMC: 2818044. DOI: 10.1177/0961203307087875. View

18.

Torrente-Segarra V, Salman Monte T, Rua-Figueroa I, Sanchez-Alonso F, Lopez-Longo F, Galindo-Izquierdo M . Juvenile- and adult-onset systemic lupus erythematosus: a comparative study in a large cohort from the Spanish Society of Rheumatology Lupus Registry (RELESSER). Clin Exp Rheumatol. 2017; 35(6):1047-1055. View

19.

Bortoluzzi A, Scire C, Bombardieri S, Caniatti L, Conti F, De Vita S . Development and validation of a new algorithm for attribution of neuropsychiatric events in systemic lupus erythematosus. Rheumatology (Oxford). 2014; 54(5):891-8. DOI: 10.1093/rheumatology/keu384. View

20.

Brunner H, Gladman D, Ibanez D, Urowitz M, Silverman E . Difference in disease features between childhood-onset and adult-onset systemic lupus erythematosus. Arthritis Rheum. 2008; 58(2):556-62. DOI: 10.1002/art.23204. View

21.

Soybilgic A . Neuropsychiatric Systemic Lupus Erythematosus in Children. Pediatr Ann. 2015; 44(6):e153-8. DOI: 10.3928/00904481-20150611-11. View