Age at onset has been shown to affect the clinical course and outcome of systemic lupus erythematosus (SLE). Herein, we aimed to define the differences in clinical characteristics, organ damage, and survival between patients with juvenile-onset (jSLE) and adult-onset SLE (aSLE).

For the study, 719 patients (76.9%) with aSLE and 216 (23.1%) with jSLE were examined. Comparisons between the groups were made for demographic characteristics, clinical features, auto-antibody profiles, damage, and survival rates.

These results were significantly more frequent in jSLE: photosensitivity, malar rash, oral ulcers, renal involvement, neuropsychiatric (NP) manifestations, and autoimmune hemolytic anemia (AIHA). Of the autoantibodies, a higher frequency of anti-dsDNA and anticardiolipin IgG and IgM were observed in the jSLE group. A significant proportion of patients with aSLE had anti-Sm positivity and pleuritis. The proportion of patients with jSLE who developed organ damage was comparable to that of patients with aSLE (53% vs 47%) and the mean damage scores were similar in both groups. Renal damage was significantly more frequent in jSLE while musculoskeletal and cardiovascular system damage and diabetes mellitus were more prominent in aSLE. Comparison of survival rates of the 2 groups did not reveal any significant differences.

We report a higher frequency in the jSLE group of renal involvement, cutaneous symptoms, oral ulcers, NP manifestations, AIHA, and anti-dsDNA positivity. A significant proportion of patients in the jSLE group had damage, most prominently in the renal domain. Our findings might support different genetic/environmental backgrounds for these 2 subgroups.

To determine whether there is an association between the profile of cognitive dysfunction and academic outcomes in patients with juvenile systemic lupus erythematosus (JSLE).

Patients aged ≤18 years at the onset of the disease and education level at or above the fifth grade of elementary school were selected. Cognitive evaluation was performed according to the American College of Rheumatology (ACR) recommendations. Symptoms of anxiety and depression were assessed by Beck scales; disease activity was assessed by Systemic Lupus Erythematosus Disease Activity Index (SLEDAI); and cumulative damage was assessed by Systemic Lupus International Collaborating Clinics (SLICC). The presence of autoantibodies and medication use were also assessed. A significance level of 5% (p<0.05) was adopted.

41 patients with a mean age of 14.5±2.84 years were included. Cognitive dysfunction was noted in 17 (41.46%) patients. There was a significant worsening in mathematical performance in patients with cognitive dysfunction (p=0.039). Anxiety symptoms were observed in 8 patients (19.51%) and were associated with visual perception (p=0.037) and symptoms of depression were observed in 1 patient (2.43%).

Patients with JSLE concomitantly with cognitive dysfunction showed worse academic performance in mathematics compared to patients without cognitive impairment.

We have previously shown that children with pediatric systemic lupus erythematosus (pSLE) have high incidence of anti-phospholipid antibodies (APLA) and reports suggest that presence of APLA can modify disease expression. While the frequency of APLA has been studied previously in adults with SLE, there is paucity of literature in children especially with regard to long-term follow-up. In the earlier study, we analyzed 27 pSLE patients for the prevalence of APLA; in the present study, we further reviewed the APLA status and its relation with clinical outcome of this cohort of patients over a further 7 year follow-up period. Out of the initial cohort of 27 patients, follow-up APLA testing was available in 21 patients who were tested for APLA at least once during this time. Seven (33.3 %) of these 21 patients were never positive for any of the APLA; 1 (4.8 %) was persistently positive; and 13 (61.9 %) were positive for APLA intermittently or at least once. Overall, APLA positivity for IgG, IgM anticardiolipin antibodies (ACA) and lupus anticoagulant (LA) was comparable, with positivity seen in 10 (47.6 %), 9 (42.9 %) and 9 (42.9 %) cases, respectively. Anti-β2 GP1 antibodies were tested in 11 patients on follow-up, of which 3 (27.3 %) showed positivity. In all, 10 (47.6 %) patients showed positivity for more than 1 APLA. Two (9.5 %) patients showed varying degrees of positivity for LA, ACA, and anti-β2 GP1 antibodies at different times, thereby showing the importance of checking for all APLAs at each time of testing. Out of these 21 patients, 3 (14.3 %) patients had thrombosis, and all 3 patients were positive for APLA. There were 2 (9.5 %) fatalities-both of these had thrombosis and were positive for APLA. Our study shows that pSLE patients on treatment frequently test positive for APLA. Thrombosis was infrequent in this cohort. However, when present it was associated with APLA positivity and high fatality in our experience. On the other hand, presence or persistence of these antibodies was not always associated with thrombosis. Our study suggests that pSLE children should be tested routinely for APLA, as this would identify patients with an increased risk of thrombotic complications. However, the frequency of repeat testing for APLA in those who test negative initially needs to be determined on a case-to-case basis.

Lupus nephritis (LN) is more common and severe in childhood-onset systemic lupus erythematosus (SLE) than in adults. It is one of the major causes of acute kidney injury (AKI) and chronic kidney disease (CKD) in children. Steroid therapy has been used as the first-line treatment for SLE since 1970, and has improved the survival of SLE patients from ∼ 50% to >80%. Over the years many immunosuppressive drugs, including pulse methylprednisolone, oral cyclophosphamide, pulse intravenous cyclophosphamide, mycophenolate mofitil, rituximab, and tacrolimus, have been combined with prednisolone, further improving survival rates to 90%-95%. However, the effectiveness of these drugs is still uncertain, as most seem very good in the beginning, but in studies examining longer-term follow-up the remission of disease does not remain. Fatal infection is still a major complication of aggressive chemotherapy, and the potential benefits as well as adverse events from each drug need to be considered. Induction of remission is the major aim of therapy, with safe and effective maintenance therapy for long-term remission. The survival rates of many published studies vary widely because of differences in patients and treatment modalities, severity of disease, renal histopathology, racial factors, and duration of follow-up. Finding the optimal treatment for SLE and related co-morbidities is highly challenging, and will likely involve a complex combination of different drugs for different patients in the search for giving them an opportunity to be free from this debilitating disease.

To determine the serum levels of Th1 (IL-12, IFN-γ,TNF-α) and Th2 (IL-5, IL-6 and IL-10) cytokines in childhood-onset SLE, first-degree relatives and healthy controls. To elucidate their association with disease activity, laboratory and treatment features.

We included 60 consecutive childhood-onset SLE patients [median age 18 years (range 10-37)], 64 first-degree relatives [median 40 (range 28-52)] and 57 healthy [median age 19 years (range 6-30 years)] controls. Controls were age and sex-matched to SLE patients. SLE patients were assessed for clinical and laboratory SLE manifestations, disease activity (SLEDAI), damage (SDI) and current drug exposures. Mood and anxiety disorders were determined through Becks Depression (BDI) and Anxiety Inventory (BAI). Th1 (IL-12, IFN-γ,TNF-α) and Th2 (IL-5, IL-6 and IL-10) cytokines levels were measured by ELISA and compared by non-parametric tests.

Serum TNF-α (p=0.004), IL-6 (p=0.007) and IL-10 (p=0.03) levels were increased in childhood-onset SLE patients when compared to first-degree relatives and healthy controls. TNF-α levels were significantly increased in patients with active disease (p=0.014) and correlated directly with SLEDAI scores (r=0.39; p=0.002). IL-12 (p=0.042) and TNF-α (p=0.009) levels were significantly increased in patients with nephritis and TNF-α in patients with depression (p=0.001). No association between cytokine levels and SDI scores or medication was observed.

Th1 cytokines may play a role in the pathogenesis of neuropsychiatric and renal manifestations in childhood-onset SLE. The correlation with SLEDAI suggests that TNF-α may be a useful biomarker for disease activity in childhood-onset SLE, however longitudinal studies are necessary to determine if increase of this cytokine may predict flares in childhood-onset SLE.

To determine the serum levels of interferon alpha in childhood-onset systemic lupus erythematosus patients, their first-degree relatives and healthy controls and to evaluate the associations between serum interferon alpha and disease activity, laboratory findings and treatment features.

We screened consecutive childhood-onset systemic lupus erythematosus patients in a longitudinal cohort at the pediatric rheumatology unit of the State University of Campinas between 2009 and 2010. All patients demonstrated disease onset before the age of 16. Disease status was assessed according to the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus International Collaborating Clinics/American College of Rheumatology Damage Index (SDI). Interferon alpha levels were measured using an enzyme-linked immunoabsorbent assay.

We included 57 childhood-onset systemic lupus erythematosus patients (mean age 17.33 ± 4.50), 64 first-degree relatives (mean age 39.95 ± 5.66), and 57 healthy (mean age 19.30 ± 4.97) controls. Serum interferon alpha levels were significantly increased in childhood-onset systemic lupus erythematosus patients compared to their first-degree relatives and healthy controls. Interferon alpha levels were significantly increased in patients with positive dsDNA antibodies, patients with cutaneous vasculitis, patients with new malar rash and patients who were not receiving medication. Interferon alpha levels correlated with C3 levels and systemic lupus erythematosus Disease Activity Index scores. In addition, we observed an inverse correlation between patient age and interferon alpha levels.

Interferon alpha may play a role in the pathogenesis of childhood-onset systemic lupus erythematosus, especially in cutaneous manifestations and dsDNA antibody formation. The observation that interferon alpha levels are increased in patients who are not taking medication should be investigated in longitudinal studies to determine whether elevated interferon alpha levels may predict systemic lupus erythematosus flares.