Clinical and laboratory characteristics in juvenile-onset systemic lupus erythematosus across age groups

Abstract

Background Systemic lupus erythematous (SLE) is a systemic autoimmune/inflammatory condition. Approximately 15–20% of patients develop symptoms before their 18th birthday and are diagnosed with juvenile-onset SLE (JSLE). Gender distribution, clinical presentation, disease courses and outcomes vary significantly between JSLE patients and individuals with adult-onset SLE. This study aimed to identify age-specific clinical and/or serological patterns in JSLE patients enrolled to the UK JSLE Cohort Study. Methods Patient records were accessed and grouped based on age at disease-onset: pre-pubertal (≤7 years), peri-pubertal (8–13 years) and adolescent (14–18 years). The presence of American College of Rheumatology (ACR) classification criteria, laboratory results, disease activity [British Isles Lupus Assessment Group (BILAG) and Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2 K) scores] and damage [Systemic Lupus International Collaborating Clinics (SLICC) damage index] were evaluated at diagnosis and last follow up. Results A total of 418 JSLE patients were included in this study: 43 (10.3%) with pre-pubertal disease onset; 240 (57.4%) with peri-pubertal onset and 135 (32.3%) were diagnosed during adolescence. At diagnosis, adolescent JSLE patients presented with a higher number of ACR criteria when compared with pre-pubertal and peri-pubertal patients [pBILAG2004 scores: 9(4–20] vs. 7(3–13] vs. 7(3–14], respectively, p = 0.015] with increased activity in the following BILAG domains: mucocutaneous ( p = 0.025), musculoskeletal ( p = 0.029), renal ( p = 0.027) and cardiorespiratory ( p = 0.001). Furthermore, adolescent JSLE patients were more frequently ANA-positive ( p = 0.034) and exhibited higher anti-dsDNA titres ( p = 0.001). Pre-pubertal individuals less frequently presented with leukopenia ( p = 0.002), thrombocytopenia ( p = 0.004) or low complement ( p = 0.002) when compared with other age groups. No differences were identified in disease activity (pBILAG2004 score), damage (SLICC damage index) and the number of ACR criteria fulfilled at last follow up. Conclusions Disease presentations and laboratory findings vary significantly between age groups within a national cohort of JSLE patients. Patients diagnosed during adolescence exhibit greater disease activity and “classic” autoantibody, immune cell and complement patterns when compared with younger patients. This supports the hypothesis that pathomechanisms may vary between patient age groups.

Systemic Lupus Erythematosus in Children and Young People

“…The youngest patient group less frequently presented with leukopenia ( p = 0.002), thrombocytopenia ( p = 0.004) and/or low complement ( p = 0.002) when compared to older age groups. The present study supports the hypothesis that patients diagnosed with jSLE during adolescence may display a more ‘classic’ SLE phenotype due to variation in the pathogenic mechanisms at different ages, accounting for the more atypical SLE presentation seen in younger patients [ 20 ].…”

“…The study also showed that Black African/Caribbean jSLE patients exhibit more renal involvement and more frequently receive cyclophosphamide and rituximab during their disease course when compared to patients of other ethnicities. Similar to adult studies, jSLE was found to be more prevalent in patients from minority ethnic backgrounds, compared to the UK national census figures for prevalence of ethnic minorities in the population as a whole, with 51% of UK jSLE Cohort Study participants being Caucasian, compared with 86% of the UK population as a whole [29]. Of interest, the present study also showed higher numbers of male patients and less ANA and/or anti-dsDNA positivity among Caucasians (as compared to patients from minority ethnic backgrounds), which may be due to the presence of more 'atypical' and/or 'monogenic' disease in Caucasians [2,4,29].…”

“…Sub-analysis showed that the sensitivity of the EULAR/ACR-2019 criteria was not influenced by patient ethnicity, age or gender, whereas the sensitivity of the ACR-1997 criteria was significantly higher in non-White versus White cases [ 147 ]. Further studies are warranted to assess the performance of the EULAR/ACR-2019 criteria in children, in particular as younger children with jSLE have been shown to display less ANA positivity [ 20 ].…”

Childhood-Onset Systemic Lupus Erythematosus: Southeast Asian Perspectives

“…The onset of cSLE is reported to peak during the peri-pubertal years with a median age of onset between 11–12 years and the disease is rare under the age of 5 years [ 20 ]. In SEA, ( Table 1 ) most patients are diagnosed between the ages of 11–13 years, which is comparable with other multiethnic cohorts in the West.…”

Th Cytokine Profile in Childhood-Onset Systemic Lupus Erythematosus

“…In recent years, Th cell subsets and cytokines have been found to play an important role in the pathogenesis of SLE [9]. cSLE is often more serious than that in adults, as the probability that each organ is involved is higher, and the disease process is more dangerous than that in adults [10,11]. Therefore, the detection of cytokines in SLE patients is helpful to comprehensively understand the immune status of the body and correctly judge disease condition.…”