A Brazilian single-centre series comparision of childhood,adult and late onset Systemic lupus Erythematosus

Abstract

Background

Systemic Lupus Erythematosus (SLE) is a heterogeneous multisystem autoimmune disease, with variable severity, autoantibody profile, response to treatment, relapsing course and damage accrual. The age at disease onset may influence disease trajectory and prognosis, with remarkable differences of major organ involvement, disease activity, and prognosis. SLE clinical profile, activity indices, remission, and damage comparison were carried out in childhood-onset (cSLE), adult-onset (aSLE) and late-onset (lSLE) patients from a single-centre series.

Methods

A cross-sectional analysis reviewing the clinical profile of SLE cases seen between 2012 and 2022 and classified in 3 age-groups according to disease onset: cSLE (<18 years), aSLE (18 to 49 years) and lSLE (>=50 years), was performed. Disease activity status was assessed by PGA (0-3), SLEDAI-2K, SLE-DAS, LLDAS and DORIS criteria, and damage using SDI at the same visit were compared in those 3 age-groups.

Results

Four hundred and fifteen patients were included in the analysis: 289 (68%) aSLE, 79 (19%) cSLE, and 47 (11.3%) lSLE. Most common clinical manifestations were articular (75.2%), hematological (70.1%), cutaneous (67.9%), photosensitivity (59.3%), and renal (41.7%). The clinical profile was similar among the subgroups of SLE patients, except for lSLE with lower frequency of nephritis and serositis, lower frequency of autoantibodies and hypocomplementenemia, lower SLEDAI-2K and SLE-DAS scores, and a higher frequency of LLDAS and DORIS remission; and a higher damage scores (SDI). Patients with cSLE had a significantly higher frequency of renal and neurological involvement, and a longer disease duration, but the disease activity, damage scores and remission rates were comparable to adult-onset group.

Conclusion

The remarkable differences among the 3-age-groups were higher frequency of renal and neuropsychiatric domains in youngsters and disease activity scores compared to other age-groups. The lSLE group had less nephritis and serositis, lower disease activity and higher damage scores.

Keywords

Activity damage systemic lupus erythematosus childhood-onset SLE late-onset SLE

Introduction

Systemic Lupus Erythematosus (SLE) is a heterogeneous chronic multisystem autoimmune disease.^1,2 Its pathophysiology involves the interactions of multiple genetic, epigenetic, hormonal, environmental, and sociodemographic factors, which lead to immunological self-tolerance loss and trigger a dysregulated immune response.³ The estimated global prevalence is between 9 and 241 cases per 100,000 person-years, and incidence is between 0.3 and 23.2 per 100,000 person-years,^4,5 with marked population diversity. Although SLE is more commonly diagnosed in women of childbearing age, with onset typically between the second and fourth decades of life, it can also affect both children and the elderly.⁶

SLE multiorgan and systems involvement differ in severity, autoantibody profile, treatment response, risk of relapses, and damage accrual. Its course is often unpredictable, with a high risk of recurrence.^6,7 Treatment goals are to increase survival, promote better quality of life, and prevent damage. In recent years, the importance of early treatment has been increasingly emphasized, highlighting the adoption of prompt ‘treat-to-target' approach, which involves actively searching clinical and laboratory targets combined with strategies to minimize the risk of flares.^8,9 In this context, multiple targets and definitions have been proposed, among which the most widely used are the definition of remission in SLE (DORIS) and the Lupus Low Disease Activity State (LLDAS),^10,11 both associated with a lower risk of flares, damage accrual and mortality.

The prognosis of patients with SLE has historically improved due to earlier diagnosis, advances in treatment, and effective management of comorbidities. Nevertheless, patients with SLE continue to exhibit a mortality rate approximately 2 to 5 times higher than that of the general population, with a 15-year survival rate estimated of 76 to 85%. Disease onset age is an important modulating factor of the course and prognosis with differences in major organ involvement, disease activity, and prognostic factors.^12,13 Previous studies described the clinical and laboratory characteristics of Brazilian series of patients with SLE^14,15 at different onset ages,^16,17 reporting heterogeneous findings, but more recent criteria definition for disease activity (SLE-DAS, LLDAS) and remission are lacking.

This study aimed at comparing SLE activity indices, damage and remission status among subgroups of patients with childhood-onset (cSLE), adult-onset (aSLE) and late-onset (lSLE) disease, in an outpatient cohort from a Brazilian Rheumatology referral center.

Method

A cross-sectional study was conducted through the analysis of electronic medical records of all patients treated at the SLE outpatient clinic of the São Paulo State University (UNESP) Medical School (Botucatu, Brazil), between 2012 and 2022. Patients classified by at least one of the following criteria were included: revised American College of Rheumatology (ACR) criteria,¹⁸ Systemic Lupus International Collaborating Clinics (SLICC) criteria,¹⁹ or European League Against Rheumatism and American College of Rheumatology (EULAR/ACR) criteria.²⁰ A minimum follow-up time of 6 months was required. Patients not fulfilling the specified inclusion criteria, as well as those presenting with isolated cutaneous forms of the disease, were excluded. The study was reviewed and approved by the institutional ethics committee with signed informed consent from all participants.

The patients were grouped according to the age of disease onset: childhood-onset SLE (cSLE) (<18 years), adult-onset SLE (aSLE) (18 to 49 years) and late-onset SLE (lSLE) (≥50 years). Sociodemographic factors (age, gender and self-declared ethnicity), along with clinical, laboratory and autoantibody profiles, and treatments throughout the disease course, were recorded. The definitions of clinical manifestations of SLE were based on the 2012 SLICC classification criteria.¹⁹ In patients with SLE nephritis, renal biopsies were classified according to the histological class of the 2003 revised criteria by the International Society of Nephrology/Renal Pathology Society (ISN/RPS).²¹

Disease activity was assessed using the Physician Global Assessment scale (PGA 0-3),²² Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI-2K),²³ and Systemic Lupus Erythematosus Disease Activity Score (SLE-DAS),²⁴ at the last clinical visit. Disease remission was classified according to the definition of remission in SLE (DORIS)²⁵ and Lupus Low Disease Activity State (LLDAS),¹¹ as well as the damage scores according to the Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index (SDI).²⁶ Disease flare was defined as worsening of a measurable clinical and/or laboratory parameter resulting in an elevation higher than or equal 3 points in SLEDAI-2K scores, and requiring therapy adjustment.²⁷

Numerical variables were described by median with interquartile range or means and standard deviation. Categorical variables were presented as percentages. The Kruskal-Wallis test or the Student's t-test were used to compare numerical variables, depending on normal distribution. The Kolmogorov–Smirnov test was used to classify the variable distribution as parametric or non-parametric. For categorical variables, the chi-square test or Fisher’s exact test were applied where appropriate, and logistic regression was employed for multivariate analysis of the factors associated with damage and remission indices. A p-value ≤.05 was considered statistically significant. Statistical analyses were performed using the SAS software (version 9.4).

Results

From July to December 2023, 492 registered patients were identified in follow up at the SLE outpatient clinic between 2012 and 2022. Of those, 77 were excluded, mostly due to not fulfilling the SLE classification criteria (65%) or to the presence of an isolated cutaneous form (16.9%). Therefore, 415 patients were consecutively included for the analysis: 289 (68%) aSLE, 79 (19%) cSLE, and 47 (11.3%) lSLE. In the overall cohort, there was a female (91.8%) and Caucasian self-declared (80.2%) predominance, with a median age at onset and disease duration of 43 (32-45) and 11 (6-18) years, respectively. The most common clinical manifestations were articular (75.2%), hematological (70.1%), cutaneous (67.9%), photosensitivity (59.3%), and renal (41.7%).

On Table 1 there is a comparison of sociodemographic and clinical data among the 3-age groups. The sociodemographic profiles were comparable, but the late-onset group had a lower proportion of females, although this difference was not statistically significant.

Table 1.

Sociodemographic and clinical profile of SLE subgroups according to aSLE, cSLE and lSLE age groups.

Variables	aSLE (n = 289)	cSLE (n = 79)	lSLE (n = 47)	p-value
Age, years median (IQ range)	45 (35–52)	26 (22-33.5)	65 (61–70.5)	<0,0001^1,2,3
Female, n (%)	270 (93.4)	71 (89.9)	40 (85.1)	0.12
Ethnicity, n (%)
Caucasian	233 (80.6)	64 (81)	38 (80.8)	1.0
Black	19 (6.6)	5 (6.3)	0 (0)	0.2
Brown	1 (0.3%)	0 (0)	1 (2.1)	0.7
Disease duration, years median (IQ range)	11 (5–18)	12 (7.5–19)	7 (4–10.5)	0.0002^2,3
Overlap, n (%)	89 (30.8)	12 (15.2)	15 (31.9)	0.04^2,3
Sjogren disease	42 (24.3)	5 (6.3)*	9 (19.1)	0.08
Antiphospholipid syndrome	27 (9.3)	1 (1.3)*	4 (8.5)	0.01³
Rheumatoid arthritis	22 (7.6)*	7 (8.9)	4 (8.5)	0.81
Systemic sclerosis	12 (4.1)*	0 (0)	0 (0)	0.07
Comorbidities, n (%)	269 (93)	62 (78.5)	45 (95.7)	0.005^2,3
Classification criteria, n (%)
ACR (2009)	270 (93.4)	75 (94.9)	42 (89.4)	0.47
SLICC (2012)	284 (97.9)	79 (100)	47 (100)	0.33
EULAR/ACR (2019)	278 (96.2)	79 (100)	44 (93.6)	0.12
Oral ulcers, n (%)	108 (37.4)	28 (35.4)	11 (23.4)	0.17
Alopecia, n (%)	89 (30.8)	32 (40.5)	11 (23.4)	0.11
Cutaneous, n (%)	203 (70.2)	50 (63.3)	29 (61.7)	0.31
Articular, n (%)	223 (79.9)	57 (72.1)	322 (68)	0.32
Hematological, n (%)	203 (70.2)	56 (70.9)	32 (68)	0.94
AIHA, n (%)	33 (11.4)	11(13.9)	9 (19.1)	0.32
Thrombocytopenia, n (%)	52 (18)	15 (19)	11 (23.4)	0.68
Leukopenia, n (%)	104 (36)	29 (36.7)	18 (38.3)	0.95
Lymphopenia, n (%)	153 (52.9)	35 (44.3)	20 (51.1)	0.21
Neutropenia, n (%)	18 (6.2)	6 (7.6)	5 (10.6)	0.34
Renal, n (%)	118 (40.8)	52 (65.8)	3 (6.4)	<0.0001^1,2,3
Neuropsychiatric, n (%)	36 (12.4)	19 (24)	8 (17)	0.02³
Pulmonary, n (%)	57 (19.7)	10 (12.6)	7 (14.9)	0.3
Cardiovascular, n (%)	37 (12.8)	9 (11.4)	1 (2.1)	0.1
Serositis, n (%)	71 (24.5)	16 (20)	3 (6.4)	0.004^1,2
Gastrointestinal, n (%)	18 (6.2)	5 (6.3)	3 (6.4)	1.0

AIHA: autoimmune hemolytic anemia, ACR: American College of Rheumatology, EULAR: European League Against Rheumatism, SLICC: Systemic Lupus International Collaborating Clinics.

*aSLE versus lSLE; **cSLE versus lSLE; ***aSLE versus cSLE.

In general, the clinical profile was comparable among the subgroups of patients with SLE, with predominance of articular, cutaneous, and hematological involvements. The lSLE group had a lower frequency of renal involvement (6.4%) and serositis (6.4%), as well as a tendency toward less cardiac involvement (2.1%). Furthermore, the lSLE group had lower frequency of ANA (antinuclear antibodies), anti-dsDNA (double-stranded DNA), anti-Sm (Smith), and anti-RNP (ribonucleoprotein) antibodies, besides lower serum complement components (C3 and C4) (Table 2). There were no differences regarding the positivity of other autoantibodies, including antiphospholipid antibodies. Patients with cSLE had less comorbidities or other autoimmune disease overlap and showed a significantly higher frequency of renal (65.8%) and neuropsychiatric (24%) involvement.

Table 2.

Laboratory and immunological profile of patients with SLE according to aSLE, cSLE and lSLE age groups.

Laboratory markers	aSLE (n = 289)	cSLE (n = 79)	lSLE (n = 47)	p-value
ANA, n (%)	288 (99.6)	78 (98.7)	45 (95.7)	0.05^a,b
Anti-dsDNA, n (%)	230 (79.6)	66 (83.5)	35 (74.5)	0.05
Anti-sm, n (%)	81 (28)	27 (34.2)	3 (6.4)	0.0001^a,c
Anti-RNP, n (%)	81 (28)	21 (26.6)	5 (10.6)	0.001^a,c
Low C3 or C4, n (%)	217 (75.1)	68 (86)	31 (65.9)	0.01^c,b
LAC, n (%)	31 (10.7)	11 (13.9)	4 (8.5)	0.6
aCL IgM, n (%)	28 (9.7)	8 (10.1)	4 (8.5)	0.9
aCL IgG, n (%)	22 (7.6)	7 (8.9)	5 (10.6)	0.8
Coombs, n (%)	63 (21.8)	19 (24)	8 (17)	0.65
Anti-Ro, n (%)	109 (37.8)	22 (27.8)	21 (44.7)	0.13
Anti-La, n (%)	37 (12.8)	13 (16.4)	4 (8.5)	0.11
Rheumatoid factor, n (%)	56 (19.4)	11 (13.9)	12 (25.5)	0.27
Anti-CCP, n (%)	4 (1.4)	0 (0)	1 (2.1)	0.5

ANA: Anti-nuclear antibodies, aCL: anticardiolipin, LAC: lupus anticoagulant, CCP: Cyclic Citrullinated Peptide.

^aaSLE versus lSLE.

^ccSLE versus lSLE.

^baSLE versus cSLE.

The cross-sectional assessment of disease and clinical parameters are summarized in Table 3. Patients with lSLE presented a higher frequency of remission, fulfilling LLDAS and DORIS criteria, and lower SLEDAI-2K and SLE-DAS scores. In contrast, they showed a higher damage score (SDI), in particular when categoric comparison was made (0 or ≥1). On the other hand, patients with cSLE had a longer disease duration, although comparable disease activity, damage and remission rates compared to the aSLE group. Multivariate logistic regression analysis, adjusted by clinically relevant variables (gender, ethnicity, disease duration and comorbidities), revealed that lSLE was an independent factor associated with higher damage accrual (SDI ≥1), although association for achieving DORIS criteria was retained only when compared to cSLE group (Table 4). No statistically significant association was found between lSLE and achievement of LLDAS after adjustment. Additionally, disease duration and presence of hypertension were also identified as independent risk factors for damage.

Table 3.

Disease activity and outcome measures of patients with SLE according to aSLE, cSLE and lSLE age groups.

Parameters	aSLE (n = 289)	cSLE (n = 79)	lSLE (n = 47)	p-value
Last visit status, n (%)
Remission	144 (49.8)	37 (46.8)	31 (65.5)	0.08
Controlled	88 (30.4)	34 (43)	13 (27.6)	0.08
Flare	49 (16.9)	7 (8.9)	3 (6.3)	0.05
LLDAS, n (%)	209 (72.3)	52 (65.8)	41 (87.2)	0.001^a,b
Remission (DORIS), n (%)	133 (46)	30 (38)	28 (59.6)	0.01^b
SLEDAI-2K, Md (IQ range)	2 (0-4)	2 (0-4)	0 (0-2)	0.04^b
SLE-DAS, Md (IQ range)	1.1 (0.4-4.5)	1.3 (0.4-4.6)	0.4 (0.4-2.1)	0.07
PGA (0-3), Md (IQ range)	0 (0-0.5)	0 (0-0.5)	0 (0-0.5)	0.28
SDI, Md (IQ range)	1 (0-2)	1 (0-2)	1 (1-2)	0.05^a,b
SDI ≥1, n (%)	171 (59.2)	41 (51.2)	37 (78.7)	0.01^a,b

DORIS: definition of remission in Systemic Lupus Erythematosus, SLEDAI-2K: Systemic Lupus Erythematosus Disease Activity Index 2000, SLE-DAS: Systemic Lupus Erythematosus Disease Acitivity Score, PGA: Phisician global assessment, LLDAS: Lupus Low Disease Activity State, SDI: Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index.

^aaSLE versus lSLE.

^bcSLE versus lSLE.

^caSLE versus cSLE.

Table 4.

Multivariate logistic regression analysis of factors associated with damage and remission indices in patients with SLE.

	SDI (≥1)		DORIS		LLDAS
Variables	OR (CI 95%)	p-value	OR (CI 95%)	p-value	OR (CI 95%)	p-value
SLE group
lSLE vs aSLE	2.87 (1.34-6.16)	0.01	1.72 (0.92-3.24)	0.09	2.61 (1.07-6.4)	0.04
lSLE vs cSLE	2.41 (1.15-5.0)	<0.01	2.41 (1.15-5.04)	0.02	3.55 (1.33-9.4)	0.01
SLE group^a
lSLE vs aSLE	2.95 (0.99-8.71)	0.05	1.48 (0.63-3.45)	0.36	1.71 (0.57-5.11)	0.34
lSLE vs cSLE	4.14 (1.26-13.65)	0.02	2.81 (1.04-7.6)	0.04	2.97 (0.89-9.82)	0.07
Disease duration^a	0.95 (0.92-0.99)	0.001
Hypertension^a	2.1 (1.18-3.7)	0.01

CI: Confidence interval, DORIS: definition of remission in Systemic Lupus Erythematosus, LLDAS: Lupus Low Disease Activity State, OR: Odds ratio, SDI: Systemic Lupus International Collaborating Clinics/American College of Rheumatology (SLICC/ACR) Damage Index.

^aAdjusted for gender, ethnicity, disease duration, hypertension and diabetes.

Treatment received during the entire disease course indicated lower frequency of azathioprine, cyclophosphamide, mycophenolate, rituximab, and methylprednisolone pulses use in patients with lSLE, along with a trend towards less hydroxychloroquine use. Conversely, patients with cSLE were more likely to receive cyclophosphamide, azathioprine, mycophenolate, methylprednisolone pulses, and hydroxychloroquine. No significant differences were observed in the frequency or dosages of oral corticosteroids. The relative frequency of immunossupressive and biological treatments is described in Table 5.

Table 5.

Cumulative treatment of patients with SLE according to aSLE, cSLE and lSLE age groups.

Treatments	aSLE (n = 289)	cSLE (n = 79)	lSLE (n = 47)	p-value
Hydroxychloroquine, n (%)	216 (74.7)	67 (84.8)	32 (68)	0.07
Oral prednisone, n (%)	100 (34.6)	29 (36.7)	11 (23.4)	0.26
Prednisone dose, median (IQ range)	10 (5-20)	10 (5-20)	10 (5-15)	0.58
Methotrexate, n (%)	88 (30.4)	21 (26.6)	9 (19.1)	0.26
Cyclosporine, n (%)	12 (4.1)	5 (6.3)	1 (2.1)	0.49
Azathioprine, n (%)	137 (47.4)	50 (63.3)	11 (23.4)*	<0.0001^a,b,c
Leflunomide, n (%)	19 (6.6)	3 (3.8)	0 (0)	0.14
Cyclophosphamide, n (%)	99 (34.2)	40 (50.6)	5 (10.6)*	<0.0001^a,b,c
Rituximab, n (%)	25 (8.6)	9 (11.4)	0 (0)	0.07
Mycophenolate, n (%)	32 (11.1)	18 (22.8)	1 (2.1)*	00,1^b,c
Intravenous methylprednisolone pulse, n (%)	139 (48.1)	54 (68.3)	11 (23.4)*	<0.0001^a,b,c
Number of pulses, median (IQ range)	0 (0-1)	1 (0-2.5)	0 (0-0)	p < .0001^a,b,c

^aaSLE versus lSLE.

^bcSLE versus lSLE.

^caSLE versus cSLE.

Discussion

Our report of a higher frequency of remission, current lower rates of activity and higher damage scores in lSLE compared to aSLE and cSLE highlights the special needs of each age groups. In fact, cSLE had higher prevalence of renal and neuropsychiatric involvement, but with disease activity, damage scores and remission rates comparable to those observed in aSLE.

Despite its higher incidence in women during the reproductive age, SLE can present at any age, with variable frequency across the studies.^12,13 In the present study, 19% and 11.3% of patients had childhood-onset (<18 years) and late-onset (>50 years) SLE, respectively. These findings align with the majority of reported series of age-group comparisons.¹² Several studies evaluated the impact of onset age, clinical presentation, disease progression, and prognosis, but a remarkable heterogeneity still remains.^28–31 In a large series from Asia, Sohn et al. reported lower disease activity, SLEDAI-2K and standardized mortality ratio in the late-onset subgroup, despite no significant differences in involvement in major organs or SDI scores. More recently in a multi-center cohort at Cairo, Medhat et al. reported significantly lower mucocutaneous, serositis, renal and neuropsychiatric involvement, hypocomplementemia, SLEDAI-2K and SDI scores in late-onset SLE patients compared to childhood and adult onset, but with higher anti-dsDNA frequency and no difference of death rates.

Late-onset SLE accounts for 2–20% of all SLE cases, lacking a universally accepted age cutoff Definition.^12,32 We adopted an age cutoff of 50 years or older, the most widely used definition, that has shown no significant differences in key clinical outcomes when compared to alternative age thresholds, such age over 60-65 years.³³ Despite this heterogeneity, most studies described a more indolent clinical presentation of lSLE, with lower rates of major organ involvement, lower disease activity, and less frequent use of immunosuppressive drugs.^{13,16,30,34,35} However, lSLE is consistently associated with a higher prevalence of comorbidities, more damage accrual measured by the SDI, and increased mortality risk.^12,28,29 Our findings corroborate these observations, showing a lower frequency of nephritis, positive autoantibodies, lower complement components, and disease activity in the lSLE group. Although unadjusted data suggested higher remission and LLDAS rates, and less immunosuppressive treatment among patients with lSLE, multivariate analysis confirmed a significant association between lSLE and DORIS remission only in comparison with cSLE. No significant association with LLDAS was retained after adjustment. Nonetheless, SDI scores were consistently higher in the lSLE group on multivariate analysis, particularly when a categorical analysis (0 and ≥1) was performed. Several studies have previously reported laboratory and serological differences in lSLE, despite considerable heterogeneity.^12,29,30 Our findings likely reflect the lower clinical activity and milder disease observed in the lSLE group, alongside the relatively smaller sample size and potential influences of age-related immunosenescense. These are important considerations for future prospective studies, as a lower frequency of positive autoantibodies and complement consumption in lSLE could have significant implications for disease diagnosis and monitoring.

Conversely, cSLE represents 10%–20% of SLE cases, it is associated with higher rates of renal, neuropsychiatric and cardiovascular involvement, higher disease activity scores, morbidity and mortality rates.^12,36,37 Our findings in the cSLE group are consistent with previous studies,^38–40 showing higher prevalence of renal and neuropsychiatric involvement, and more exposure to immunosuppressive treatment and pulses of methylprednisolone. Despite the differences, disease activity, remission rates, and damage accrual were comparable to aSLE. The ethnic differences and geographical variations, as well as genetic, environmental, and sociocultural factors, might explain this variability.^41–43 Diversity in the definitions and age-limits used to classify pediatric cases may have contributed to the discrepancy.⁴⁴ In this study, “childhood-onset” was defined as an age of onset less than 18 years. This definition aligns with widely accepted classifications in recent literature and is consistent with the typical age of transition from pediatric to adult rheumatology care.^41,45,46

Heterogeneity in SLE is also evident in Brazilian series from different regions of the country,^15,17,34,47 consistent with the global literature, such as a higher prevalence of renal and neuropsychiatric involvement and greater severity in patients with cSLE, as well as a milder clinical profile. However, previous studies have not identified differences in immunological profiles or damage accrual between these groups. In contrast, our findings revealed a lower frequency of positive autoantibodies and higher damage accrual in the lSLE group. Compared to previous Brazilian series, our study showed lower rates of cutaneous and articular involvement, higher prevalence of nephritis and hematological manifestations.^14,15 These differences may be attributed to geographical and environmental diversity and climate variation, ethnic and social diversity, and disparity in healthcare access and availability of rheumatology centers.^48,49 Brazil, in particular, exhibits significant geographical and climatic diversity, which underscores the potential value of future location-based studies investigating age-related and regional differences in disease expression. In most studies, ethnicity is a factor associated with disease severity, and our cohort predominantly comprised individuals of self-identified Caucasian ethnicity. However, it is important to recognize that the Brazilian population is characterized by a high degree of genetic admixture and sociocultural heterogeneity. Ethnic classification in Brazil is largely based on self-identification, which may limit comparability with populations from countries or regions that are more genetically homogeneous.

We observed low overall disease activity and high rates of patients achieving LLDAS and remission by DORIS criteria, particularly in the lSLE group. Previous studies about SLE pathogenesis and novel therapy development emphasized the importance of early disease control, flares prevention and minimization of drug toxicity, specially from glucocorticoids exposure.^1,50 Nevertheless, previous studies demonstrated that up to 22% of patients with SLE achieve at least one point on the SDI within the first year of diagnosis, and that early damage is associated with a higher risk of progression and mortality.^12,50 Indices of disease remission are strongly correlated with the prognosis of SLE, and recently, the achievement of LLDAS within the first 6 months of disease onset, followed by its maintenance for 12 months or longer, has been associated with a reduced risk of damage and death.¹² Recently approved therapies - such as belimumab, anifrolumab and voclosporin – have demonstrated improved outcomes across various clinical settings and may change the disease course and damage accrual, particularly when initiated early.⁴ This is a critical consideration in contexts like Brazil, where access to novel therapies remains limited, especially in low-income areas.

Our study has limitations of a single-center clinical sample, retrospective data collection, and the cross-sectional design. Data was obtained from electronic medical records, and the subgroups of patients with cSLE and lSLE were relatively small for comparison. Additionally, the absence of serial data and the lack of information regarding treatment adherence and cumulative glucocorticoid doses may have influenced the results concerning disease course, mainly regarding glucocorticoids toxicity and damage accrual over time. Furthermore, the lack of registration of retrospective measures such as cumulative flares, longitudinal SLEDAI trends, or remission indices may impact the interpretation of disease control and treatment response over time. Another limitation was the absence of an analysis associating Patient-Reported Outcomes (PROs) with collected clinical data. Future longitudinal studies could incorporate PROs to provide a more comprehensive understanding about SLE outcomes. Nonetheless, this series represents a wide population from about 70 towns in provincial regions, sampling beyond metropolitan area patients referred to secondary and tertiary care, in a wide age-range and continuity of care from the pediatric to adult clinic in the same hospital. Systematic evaluations of SLE clinical features and outcome measures are in keeping with the latest guidelines and global literature results.

Conclusion

In this single-centre series of patients with SLE, those with late-onset disease exhibited less disease activity and higher damage scores measured by SDI. In contrast, patients with childhood-onset SLE showed disease activity and remission rates compared to those with adult-onset disease, but with higher prevalence of renal and neuropsychiatric involvement.

Our study provides insights about clinical characteristics of SLE across different age groups, reflecting the expression of disease in a highly populated region of a continental dimension country. Further exploratory and prospective studies will be essential for understanding the diverse factors influencing disease activity and severity across different age-groups.

Footnotes

Author contributions

The corresponding author was responsible for conducting the study and the publication. All other authors contributed equally during the study, writing and revision of the paper.

Declaration of conflicting interest

The authors declared no potential conflicts of interest concerning the research, authorship, and/or publication of this article’.

Funding

The authors received no financial support for the research, authorship, and/or publication of this article.

Ethical statement

ORCID iDs

Sean Hideo Shirata Lanças

Matheus Zanata Brufatto Furlan

Taciana de Albuquerque Pedrosa Fernandes

Cintia Zumstein Camargo

Data Availability Statement

The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.*

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