Late-onset Systemic Lupus Erythematosus Research Articles

Characteristic features of late-onset systemic lupus erythematosus: An observational study of data from the Lupus Registry of Nationwide Institutions.

Late-onset systemic lupus erythematosus (LoSLE) is known to possess characteristics different from those of early-onset SLE (EoSLE), thereby making their diagnosis difficult. This study aimed to assess the characteristic features of LoSLE in Japan, a model country with a super-aged society. Data were obtained from the Lupus Registry of Nationwide Institutions, which includes a multicenter cohort of patients with SLE in Japan who satisfied the 1997 American College of Rheumatology revised classification criteria for SLE. Data were compared between patients with LoSLE (≥50years old at onset) and EoSLE (<50years old at onset). To identify factors associated with LoSLE, binary logistic regression was used for the multivariate analysis, and missing values were complemented by multiple imputations. We also conducted a sub-analysis for patients diagnosed within 5years of onset. Out of 929 enrolled patients, 34 were excluded owing to a lack of data regarding onset age. Among the 895 remaining patients, 100 had LoSLE, whereas 795 had EoSLE. The male-to-female ratio was significantly higher in the LoSLE group than in the EoSLE group (0.32 vs 0.11, p < 0.001). With respect to SLEDAI components at onset, patients with LoSLE exhibited a higher frequency of myositis (11.9% vs 3.75%, p = 0.031), lower frequency of skin rash (33.3% vs 67.7%, p < 0.001), and lower frequency of alopecia (7.32% vs 24.7%, p = 0.012). No significant differences in overall disease activity at onset were observed between the two groups. Regarding medical history, immunosuppressants were more commonly used in EoSLE. A multivariate analysis revealed that a higher male proportion and a lower proportion of new rash at onset were independent characteristic features of LoSLE. We also identified late onset as an independent risk factor for a high SDI score at enrollment and replicated the result in a sub-analysis for the population with a shorter time since onset. We clarified that LoSLE was characterized by a higher male proportion, a lower frequency of skin rash and a tendency to organ damage. Now that the world is faced with aging, our results may be helpful at diagnosis of LoSLE.

Late Onset Systemic Lupus Erythematosus: Different Clinical, Serological Presentations and Damage Compared to Adult Lupus in Egypt

Abstract Background Comparing cases of adult onset and late onset systemic lupus erythematous (SLE) reveals significant differences in clinical, serological, disease activity, and damage score. Objective This study aimed to analyze clinical manifestations, laboratory data, serological markers, and prognosis of late-onset SLE (L-SLE) and for comparing with adult- onset SLE. Patients and Methods One hundred fifty individuals with SLE were included in a cross-sectional study conducted at Ain Shams University Hospital divide into Group 1: 100 cases with adult-onset (age of onset ≥ 19 years and below 50 years). Group 2: 50 Patients with L-SLE (age of onset ≥ 50 years). All patients were subjected to medical history, physical examination, disease activity measured by the SLE disease activity index (SLEDAI-2K) and a damage score. Laboratory investigations as complete blood count (CBC), serum creatinine, anticardiolipin antibodies, lupus anticoagulant, protein creatinine ratio, serum complement (C3, C4), anti-dsDNA antibody, and antinuclear antibodies (ANA). Results Mucocutaneous manifestations, frequency of hematuria, proteinuria, urinary cast, consumed C3, positive anti-dsDNA antibodies, anti-cardiolipin antibody and lupus anticoagulant titers had considerably greater rates in-group 1 compared to group 2 (P-value &amp;lt;0.05) while group 2 had significantly more musculoskeletal symptoms (P-value &amp;lt;0.05). The SLEDAI scores of the two groups were equivalent, however the damage index was greater in group 2 (P-value 0.00). Neuropsychiatric, cutaneous, renal, and skin damage were more frequent in group 1, while musculoskeletal, endocrinal, pulmonary, cardiovascular and ocular damage were more frequent in- group 2. Conclusion L-SLE is different from adult onset SLE with more frequent damage.

Pancytopenia as a manifestation of late-onset systemic lupus erythematosus in an older patient: a case report

Pancytopenia as a manifestation of late-onset systemic lupus erythematosus in an older patient: a case report

#1505 Late-onset lupus nephritis: clinical-epidemiological, histological, prognostic and therapeutical implications: a single center experience

Abstract Background and Aims Systemic lupus erythematosus (SLE), a chronic autoimmune disease, and lupus nephritis (LN), are typically diagnosed in women in fertile age. Late-onset SLE is defined as a disease onset over 50 years. Our main objective was to analyze the clinical, histological, prognostic and therapeutical features related to LN in our late-onset SLE population. Method A single center and retrospective study was performed comparing clinical-demographic, histological, prognostic and therapeutical data of 45 LN biopsied patients from 1994 to 2023. We divided the study population according to the age of onset of LN into classic-onset (&amp;lt; 45 years) and late-onset (&amp;gt; 45 years). Results Late-onset LN patients showed a higher association with Sjögren's and antiphospholipid syndrome, more cardiovascular comorbidities at presentation, poorer renal function at diagnosis and higher SDI score. On histology they showed more non-proliferative LN classes (II followed by V). Late-onset LN responders needed more time to achieve response but had fewer relapses. Non responsive patients had more incidence of acute kidney injury (AKI) and more glomerulosclerosis and interstitial fibrosis-tubular atrophy (IFTA) at presentation, as well as more need for renal replacement therapy (RRT) at diagnosis and at follow-up. The principal independent variables associated with relapse were the younger age at SLE diagnosis and an initial partial renal response (PRR). Patients of both groups who experienced relapse received higher doses of intravenous cyclophosphamide and less mycophenolic acid (MFA) analogues. Patients who received induction with MFA analogues were more likely to achieve complete renal response (CRR) or non-renal response (NRR). Conclusion late-onset LN is often accompanied by poor renal function at presentation. It seems imperative to establish a tailored approach in this fragile population in order to avoid unnecessary immunosuppression.

P152 Very Late Onset Systemic Lupus Erythematosus - Comparison with Younger Patients

Abstract Background/Aims Age has a significant impact on SLE. However, data on very late onset SLE (vlSLE) patients are scarce. We have characterized a large SLE patient cohort, followed for up to 45 years and compared the clinical and serological features at the different ages at diagnosis, focusing on those whose disease began at 60 or later. Methods We conducted an observational cross-sectional study at our SLE clinic. All patients with an SLE diagnosis evaluated from January 1978 to May 2023 were included. Patients were divided into four groups according to age at diagnosis: juvenile SLE (jSLE - &amp;lt;18 years); adult SLE (aSLE - 18-49 years); late SLE (lSLE - 50-59 years); vlSLE (≥ 60 years). Proportions and median values were compared using the X2 and Kruskall-Wallis tests, respectively. The probability of survival was estimated using the Kaplan-Meier method. Results 845 patients were enrolled. jSLE, aSLE, lSLE, and vlSLE groups included 153 (18.1%), 630 (74.6%), 47 (5.56%), and 15 (1.78%) patients, respectively. The mean age at diagnosis in vlSLE patients was 66.7 years. The female-to-male ratio tended to fall in the vlSLE group (4:1; p=0.282). vlSLE patients were mainly caucasian (93.3%; p&amp;lt;0.001) and had the lowest survival time (20.3 years; p&amp;lt;0.001). The most frequent clinical feature at follow-up in all groups was arthritis. Nevertheless, arthritis was least common among vlSLE patients (73.3%; p=0.043). Although malar and/or discoid rash, photosensitivity, and alopecia were less frequent among lSLE and vlSLE patients, the difference was not statistically significant. In contrast, oral ulcers tended to be more frequent in vlSLE patients (33.3%; p=0.537). vlSLE patients more commonly developed Sjögren’s syndrome (SS - 33.3%; p&amp;lt;0.001) and rheumatoid arthritis (RA - 13.3%; p&amp;lt;0.001). The prevalence of anti-phospholipid syndrome did not differ significantly between age groups. Neuropsychiatric involvement, and myositis did not occur among vlSLE patients. At diagnosis, vlSLE patients had the lowest prevalence of positive anti-dsDNA antibodies (26.7%; p=0.010) and low C3 levels (13.3%; p&amp;lt;0.001). Anti-SSA/Ro antibody positivity was also least common among vlSLE patients (26.7%; p=0.045). Although vlSLE patients also tended to have the lowest levels of ANA and anti-SSB/La antibody positivity, the difference was not statistically significant. Rheumatoid factor levels tended to increase with increasing age (p=0.066). Conclusion We report a detailed analysis of a large SLE under long term follow-up focusing on age at diagnosis related differences. Elderly patients differ from younger patients in clinical presentation. In vlSLE, female predominance is less pronounced; arthritis, anti-dsDNA antibodies and low C3 levels are less frequent. Concomitant SS and RA are more common. Our results confirm that older-onset SLE patients have lower disease activity. Nevertheless, these patients have the lowest survival rate. While very uncommon, SLE should not be excluded as a possible diagnosis in the elderly. Disclosure L. Viveiros: None. A. Neves: None. D.A. Isenberg: None.

Comparison of late-onset and non-late-onset systemic lupus erythematosus individuals in a real-world electronic health record cohort.

Objective: Late-onset systemic lupus erythematosus (LO-SLE) is defined as SLE diagnosed at age 50 years or later. Current studies on LO-SLE are small and have conflicting results.Methods: Using a large, electronic health record (EHR)-based cohort of SLE individuals, we compared demographics, disease characteristics, SLE-specific antibodies, and medication prescribing practices in LO (n = 123) vs. NLO-SLE (n = 402) individuals.Results: The median age (interquartile range) at SLE diagnosis was 60 (56-67) years for LO-SLE and 28 (20-38) years for NLO-SLE. Both groups were predominantly female (85% vs. 91%, p = 0.10). LO-SLE individuals were more likely to be White than NLO-SLE individuals (74% vs. 60%, p = 0.005) and less likely to have positive dsDNA (39% vs. 58%, p = 0.001) and RNP (17% vs. 32%, p = 0.02) with no differences in Smith, SSA, and SSB. Autoantibody positivity declined with increasing age at SLE diagnosis. LO-SLE individuals were less likely to develop SLE nephritis (9% vs. 29%, p < 0.001) and less likely to be prescribed multiple classes of SLE medications including antimalarials (90% vs. 95%, p = 0.04), azathioprine (17% vs. 31%, p = 0.002), mycophenolate mofetil (12% vs. 38%, p < 0.001), and belimumab (2% vs. 8%, p = 0.02).Conclusion: LO-SLE individuals may be less likely to fit an expected course for SLE with less frequent positive autoantibodies at diagnosis and lower rates of nephritis, even after adjusting for race. Understanding how age impacts SLE disease presentation could help reduce diagnostic delays in SLE.

Comparison of Clinical Features, Treatment and Outcomes of Lupus Nephritis Between Patients With Late- and Early-Onset Systemic Lupus Erythematosus: A Controlled Study.

Studies have found that late-onset systemic lupus erythematosus (SLE) patients (age at diagnosis ≥ 50 years) had less severe disease and milder clinical course, but with higher organ damage and mortality rate than early-onset ones (age at diagnosis < 50 years). Unfortunately, direct comparison of renal manifestations and treatment outcomes between late- and early-onset SLE patients has been determined rarely. This study aimed to compare lupus nephritis (LN) manifestations, treatment, and outcomes between late- and early-onset in SLE patients. Medical records of SLE patients in a lupus cohort at a tertiary care university hospital, seen between January 1994 and June 2020, were reviewed. Late- and early-onset patients were matched with year at SLE diagnosis at a ratio of 1:2 (62 and 124 patients, respectively). Those with LN were identified and analyzed. At SLE onset and end of the study, LN was identified in 29 and 33 late-onset patients, respectively, and 58 and 90 early-onset patients, respectively. At the end of the study, there were 39 and 214 LN flares in late- and early-onset patients, respectively: giving an incident rate (IR) (95% confidence interval (CI))/100 person-years of LN and active LN flares of 2.00 (0.75 - 5.33) vs. 6.11 (4.32 - 8.64), P = 0.020, and 5.78 (2.75 - 12.12) vs. 18.28 (13.93 - 24.00), P = 0.001, respectively. Late-onset patients received a higher proportion of moderate- to high-dose corticosteroids, but fewer immunosuppressive drugs. In all LN flares, no difference existed between the two groups in serum creatinine, degree of proteinuria, and proportion of patients with nephrotic range proteinuria or rapidly progressive glomerulonephritis, and outcomes in terms of complete, partial or no-remission were similar between them. Mortality rate was higher in late-onset patients (27.27% vs. 6.67%, P = 0.004). This matched controlled study of year at SLE diagnosis showed that late-onset SLE patients had lower prevalence of LN and LN flares. Although they received fewer immunosuppressive drugs, their renal manifestations and treatment outcomes were no different from those in early-onset patients.

Late-Onset Familial Systemic Lupus Erythematosus With Lupus Nephritis in an 82-Year-Old Male: A Case Report and Literature Review.

Systemic lupus erythematosus (SLE) rarely occurs in men of any age. Late-onset SLE (typically after the age of 50) presents special challenges. We report a case of SLE with renal involvement in a very old man. The patient, who was 82 years old, presented with acute kidney injury and a family history of SLE. He was diagnosed with lupus nephritis based on clinical criteria, although no renal biopsy was performed. After starting corticosteroid therapy, his condition improved markedly, with recovery of renal function and resolution of proteinuria and hematuria. The patient's case is notable for its advanced age and familial context, with a milder form of lupus compared with his relatives. Despite the absence of severe kidney damage, the patient's treatment with corticosteroids was effective, reflecting the unique and rare nature of this case.

Late Onset Systemic Lupus Erythematosus - Clinical and Autoantibody Profile and its Comparison with Young Onset Systemic Lupus Erythematosus.

The aim of the study was to determine the clinical features & autoantibody profile of patients having late onset Systemic Lupus Erythematosus (SLE) and to compare with young onset SLE due to its scarce data from India. All patients who fulfilled the 1997 ACR criteria for SLE were included. Late onset patients were >50 years of age and young onset were <50 years >18 years at the time of first SLE-related symptom. Clinical, laboratory, and autoantibody (ENA 25 & APLA) profiles were compared between the two groups using descriptive statistics and chi square test. Of the 305 patients, 69 had late onset (75.4% females). Mean age was 59.42±6.7 years (Late onset lupus) and 33.13±8.44 years (young onset lupus). The most common symptom was arthritis (60%) followed by oral ulceration (50%), fever (43%), and serositis (37.68%). Most common antibody was SSA/Ro60 (50%) and anti-SSA/Ro52 (46%). Interstitial lung disease (ILD) (14.5%), pancytopenia (13%) and diffuse alveolar haemorrhage (4.3%) were more frequent in late onset group. Statistically significant differences were found between two groups in terms of photosensitivity (p=0.009), malar rash (p=0.005), excessive hair loss (p=0.0006), Raynaud's phenomenon (p=0.001), lymphadenopathy (p=0.01), nephritis (p=0.0007), ILD (p=0.01), anti-dsDNA (p=0.005), anti-nucleosome (p=0.01), anti-Sm (p=0.007), Ribosomes P0 (p=0.0004). This study suggests that late onset SLE has distinct clinical and serological manifestations when compared with young onset SLE patients.

A large cohort comparison of very late-onset systemic lupus erythematosus with younger-onset patients.

Age has a significant impact on systemic lupus erythematosus (SLE). However, data on very late-onset SLE (vlSLE) are scarce. We have compared the clinical and serological features of vlSLE patients with younger-onset patients. We assessed the clinical and laboratory data of all patients fulfilling SLE classification criteria evaluated at a university hospital from 1978 to 2023. Patients were divided into 4 groups according to age at diagnosis: juvenile SLE (jSLE <8 years); adult SLE (aSLE 18-49 years); late SLE (lSLE 50-59 years); vlSLE (≥60 years). 845 patients were enrolled. The jSLE, aSLE, lSLE, and vlSLE groups included 153, 630, 47, and 15 patients, respectively. The vlSLE group tended to have a lower female-to-male ratio (4:1; p=0.282), was mainly Caucasian (93.3%; p<0.001), and had the lowest survival time (20.3 years; p<0.001). vlSLE patients had the lowest prevalence of positive anti-dsDNA antibodies (26.7%; p=0.010) and low C3 levels (13.3%; p<0.001). Although arthritis was less common among vlSLE patients (73.3%; p=0.043), they more commonly developed Sjögren's syndrome (SS 33.3%; p<0.001) and rheumatoid arthritis (RA 13.3%; p<0.001). Infections and malignancy were the main causes of death. Compared with younger patients, in vlSLE, female predominance is less pronounced. Arthritis, anti-dsDNA antibodies and low C3 levels are less frequent. SS and RA are more common. Despite lower disease activity, vlSLE patients have the lowest survival rate. While uncommon, SLE should not be excluded as a possible diagnosis in the elderly.

Neuropsychiatric lupus in late- and early-onset systemic lupus erythematosus patients: a systematic review and meta-analysis.

Late-onset SLE is usually milder and associated with lower frequency of LN and neuropsychiatric manifestations. The diagnosis of NPSLE is especially challenging in older patients because of increased incidence of neurological comorbidities. We performed a systematic review and meta-analysis to evaluate the differences in NPSLE manifestations in early-onset (<50-year-old) vs late-onset (≥50-year-old) SLE patients. A literature search was performed using the PubMed, Web of Science and Cochrane Library databases. Studies available in English (1959-2022) including a late-onset SLE comparison group and evaluating the frequency of NPSLE were eligible. A forest plot was used to compare odds ratios (95% CI) of incidence and manifestations of NPSLE by age groups. Study heterogeneity was assessed using I2 statistics. A total of 44 studies, including 17 865 early-onset and 2970 late-onset SLE patients, fulfilled our eligibility criteria. CNS involvement was reported in 3326 patients. Cumulative NPSLE frequency was higher in the early-onset group than in the late-onset group (OR: 1.41, 95% CI: 1.24, 1.59, P < 0.0001). In early-onset SLE patients, seizures (OR: 1.68, 95% CI: 1.27, 2.22) and psychosis (OR: 1.72, 95% CI: 1.23, 2.41) were more common than in late-onset SLE patients (P values, 0.0003 and 0.0014, respectively). Peripheral neuropathy was more commonly reported in the late-onset SLE group than in the early-onset SLE group (OR: 0.64, 95% CI: 0.47, 0.86, P = 0.004). Our meta-analysis revealed that the frequencies of overall NPSLE, seizures, and psychosis were less common in late-onset SLE patients than in early-onset SLE patients. In contrast, peripheral neuropathy was more common in the late-onset SLE group.

Clinicopathologic characteristics and outcomes of late onset lupus nephritis: a single centre experience.

Systemic Lupus Erythematosus (SLE) occurs in the reproductive age group. Renal involvement occurs less frequently in late-onset SLE than in reproductive-age SLE patients. Here, we aimed to study the clinical, serological and histopathological characteristics of late-onset lupus nephritis (LN). Late-onset LN was defined as disease onset after 47years of age, corresponding to the average menopausal age. Records of biopsy proven late-onset lupus nephritis patients diagnosed between June 2000 and June 2020 were reviewed. Late-onset LN constituted 53 of 4420 patients (1.2%) biopsied during the study period. Females represented 90.65% of the cohort. Mean age of the cohort was 49.5 ± 7.05years at the time of SLE diagnosis while its renal presentation was delayed by median duration of 10months (IQR 3-48months). Renal failure was present in 28 patients (52.8%) with acute kidney injury (AKI) (28.3%, n = 15) as the most common presentation. On histopathological analysis, class IV was observed in 23 patients (43.5%), crescents were observed in one-third cases and lupus vasculopathy in 4 patients (7.5%). All patients received steroids. Majority of patients (43.3%; n = 23) received Euro lupus protocol for induction. On median follow up duration of 82months, renal flares were noted in 9 patients (17%) and 8 patients (15.1%) became dialysis dependent. Among 11 patients (21%) with infectious complications, 7 patients (13.2%) suffered from tuberculosis. Infections caused three-fourth of the deaths. Late-onset lupus nephritis is rare and presents as renal failure in majority. Renal biopsy affects the clinical decision of judicious use of immunosuppression which is imperative due to high rate of infections in this cohort.

#4928 CLINICAL AND HISTOLOGICAL CHARACTERISTICS AND LONG-TERM PROGNOSIS OF LATE-ONSET LUPUS NEPHRITIS

Abstract Background and Aims Systemic lupus erythematosus (SLE) occurs mainly occurs in young women of child-bearing age and is not commonly found in the elderly population. Several studies suggest that the age at the onset of the disease has an influence on the course and the prognosis of the disease. Some studies have described that an early onset of lupus nephritis (LN) has a worse prognosis than a late-onset, presenting with greater complications and higher mortality, whereas other studies have shown that late-onset SLE present higher rate of organ damage and mortality. There are no series of late-onset LN that have been described in a European population to date. The KDIGO guidelines do not distinguish early from late-onset LN regarding their immunosuppression strategy recommendations The objective of this study was to compare the presentation, course and outcomes of late-onset LN compared to early-onset LN in a Spanish population, and detect differences in outcomes according to treatment received. Method We performed an observational retrospective multicenter study that included adult patients who developed LN confirmed by a kidney biopsy after the age of 50 years, defined as late-onset LN. We compared them to a group of selected patients aged younger than 50 years at the diagnosis (early-onset LN), matched for disease duration. Baseline demographic, clinical, serological and histological characteristics were compared between both groups. We compared the course of the disease in both groups including renal flares, serious adverse effects, and a composite outcome defined as doubling serum creatinine, developing end-stage kidney disease and/or death. Cox regression analysis was used to examine the association between late-onset LN and its outcomes. Results The study included 229 patients; 67 with late-onset LN and 162 early-onset LN patients. Late-onset LN patients presented more frequently hypertension (p&amp;lt;0.001) and diabetes (p = 0.008). There was a lower frequency of cutaneous manifestations (p &amp;lt;0.001) and oral ulcers (p = 0.008), higher frequency of hematological manifestations (p = 0.015) and Sjogren syndrome (p = 0.05). Patents with late-onset LN showed a worse baseline kidney function (p&amp;lt;0.001) and higher serum complement levels (p&amp;lt;0.001). Late-onset LN patients showed higher chronicity indices in kidney biopsies, with more glomerulosclerosis (p = 0.003), interstitial fibrosis (p = 0.021) and tubular atrophy (p = 0.011). There were no differences in the distribution of LN histological classification between both groups. We did not find significant differences between early and late-onset LN as regards induction and maintenance immunosuppression therapies, showing only a lower rate of antimalarial drug use in late-onset LN as maintenance therapy (p = 0.001). After a median follow-up of 7.4 (2.8-13) years, patients with late-onset LN showed a lower number of flares (p = 0.015), and a higher rate of serious adverse events related to immunosuppression, particularly infectious complications (34.3% vs 18.5%, p = 0.01). There were no differences in complete or partial remission or kidney function between both groups at the end of follow-up, however mortality was higher in late-onset LN patients, developing more frequently the composite outcome (19.4% vs 8%, p = 0.014). No significant difference was found in kidney survival (log-rank chi-square = 2.09, p = 0.148). Cox regression analysis showed that late-onset LN (hazard ratio = 3.26, 95% CI 1.18-8.98, p = 0.02), % sclerosed glomeruli (HR = 1.03, 95% CI 1.01-1.06, P = 0.019) and presence of severe side effects related to immunosuppression (HR = 10.09, 95% CI 3.2-31.7, p&amp;lt;0.001) were independent risk factors for reaching the composite outcome. Conclusion Although patients with late-onset LN present with worse kidney function and more severe chronic lesions in kidney biopsy, they show comparable kidney outcomes to patients with early-onset LN, and despite receiving similar immunosuppressive regimens they develop less renal flares but more serious adverse events, leading to a worse overall outcome. Minimization of immunosuppression regimens in late-onset LN may be an adequate option to improve patient outcomes.

Higher Genetic Risk Loads Confer More Diverse Manifestations and Higher Risk of Lupus Nephritis in Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a highly heritable complex disorder with heterogeneous clinical manifestations. In this study, we aimed to identify the genetic risk load using clinical and serological manifestations in SLE patients. We genotyped a total of 1,655 Korean patients with SLE (n=1,243 as a discovery set and n=412 as a replication set) using a customized genome-wide single-nucleotide polymorphism (SNP) array, KoreanChip. A weighted genetic risk score (wGRS) for an individual was calculated from 112 well-validated non-HLA SNPs and HLA haplotypes of SLE-risk loci. We analyzed associations between individual wGRS and clinical SLE subphenotypes and autoantibodies using multivariable linear or logistic regression adjusted by onset age, sex, and disease duration. Childhood-onset SLE (<16 years) conferred the highest genetic risk compared with adult-onset (16-50 years) or late-onset (>50 years) SLE (P = 6.8 × 10-6 ). High wGRS significantly increased associations with SLE manifestations, regardless of onset age, sex, and disease duration. Individual wGRS significantly correlated positively with more clinical American College of Rheumatology criteria (β=0.143, P = 1.8 × 10-6 ). Subphenotype analysis revealed significant associations between the highest and lowest wGRS quartile with risk of renal disorder (hazard ratio [HR] 1.74, P = 2.2 × 10-8 ) and anti-Sm antibody production (HR 1.85, P = 2.8 × 10-5 ). Higher wGRS markedly modulated the pathogenesis of proliferative and membranous lupus nephritis class III or IV (HR 1.98, P = 1.6 × 10-5 ) and class V (HR 2.79, P = 1.0 × 10-3 ), but especially lupus nephritis class V in anti-Sm-positive SLE (area under the curve 0.68, P = 1.8 × 10-4 ). Patients with SLE and high wGRS tended to have earlier age of SLE onset, higher anti-Sm antibody positivity, and more diverse clinical phenotypes. Genetic profiling may predict high risk for lupus nephritis and a diverse clinical course in SLE patients.

Comparison of clinical features, disease activity, treatment and outcomes between late-onset and early-onset patients with systemic lupus erythematosus. A sex- and year at diagnosis-matched controlled study

BackgroundSeveral studies have compared the clinical features and outcomes of late- and early-onset systemic lupus erythematosus (SLE) patients. However, these previous studies were uncontrolled. The current study aimed to compare late- and early-onset SLE patients while controlling for sex and year at diagnosis (± 1 year).MethodsThe medical records of SLE patients in a lupus cohort from January 1994 to June 2020 were reviewed. Late-onset patients were identified as those with an age at diagnosis ≥ 50 years. The early-onset patients (age at diagnosis < 50 years) were matched by sex and year at diagnosis with the late-onset patients at a ratio of 2:1. Clinical manifestations, disease activity (mSLEDAI-2K), organ damage scores, treatment, and mortality were compared between the two groups.ResultsThe study comprised 62 and 124 late- and early-onset patients, respectively, with a mean follow-up duration of 5 years. At disease onset, when comparing the early-onset patients with the late-onset patients, the latter group had a higher prevalence rate of serositis (37.0% vs. 14.5%, p < 0.001) and hemolytic anemia (50.0% vs. 33.9%, p = 0.034) but lower prevalence rate of malar rash (14.5% vs. 37.1%, p = 0.001), arthritis (41.9% vs. 62.1%, p = 0.009), leukopenia (32.3% vs. 50.0%, p = 0.022) and lymphopenia (50.0% vs. 66.1%, p = 0.034). The groups had similar SLE disease activity (7.41 vs. 7.50), but the late-onset group had higher organ damage scores (0.37 vs. 0.02, p < 0.001). The rates of treatment with corticosteroids, antimalarial drugs, or immunosuppressive drugs were not different. At their last visit, the late-onset patients still had the same pattern of clinically significant differences except for arthritis; additionally, the late-onset group had a lower rate of nephritis (53.2% vs. 74.2%, p = 0.008). They also had a lower level of disease activity (0.41 vs. 0.57, p = 0.006) and received fewer antimalarials (67.7% vs. 85.5%, p = 0.023) and immunosuppressive drugs (61.3% vs. 78.2%, p = 0.044), but they had higher organ damage scores (1.37 vs. 0.47, p < 0.001) and higher mortality rates/100-person year (3.2 vs. 1.1, p = 0.015). After adjusting for disease duration and baseline clinical variables, the late-onset patients only had lower rate of nephritis (p = 0.002), but still received fewer immunosuppressive drugs (p = 0.005) and had a higher mortality rate (p = 0.037).ConclusionsIn this sex- and year at diagnosis-matched controlled study, after adjusting for disease duration and baseline clinical variables, the late-onset SLE patients had less renal involvement and received less aggressive treatment, but had a higher mortality rate than the early-onset patients.

Effusive-constrictive pericarditis as first manifestation of late-onset systemic lupus erythematosus: an atypical case with grave prognosis

BackgroundSystemic lupus erythematosus (SLE) is a multisystem autoimmune disease that has a great diversity of clinical presentations and occurs mostly in young women. However, late-onset SLE does exist and seldom presents with an atypical case, including pericardial effusion (PE).Case presentationA 64 years old Asian woman presented with weakness all over the body and slight breathlessness for the past 2 days before the hospital admission. Her initial vital signs are 80/50 mmHg for blood pressure and a respiration rate of 24 breaths/min. Rhonchi were heard on the left lung and pitting edema on both legs. No evidence of any skin rash. Laboratory examination displayed anemia, hematocrit decrement, and azotemia. A 12-lead ECG demonstrated left-axis deviation with low voltage (Fig. 1). Chest X-ray showed left massive pleural effusion (Fig. 2). Transthoracic echocardiography revealed biatrial enlargement, normal EF 60%, diastolic dysfunction grade II, and thickening of the pericardium with mild circumferential PE corresponding with effusive-constrictive pericarditis (Fig. 3). The patient also brought CT angiography and cardiac MRI result, which confirmed pericarditis with PE. Treatment was initiated in ICU with fluid resuscitation of normal saline. The patient’s routine oral treatments, including furosemide, ramipril, colchicine, and bisoprolol, were carried on. An autoimmune workup was performed by a cardiologist and demonstrated an elevation in antinuclear antibody/ANA (IF) of 1:100, which finally unveiled a diagnosis of SLE. Pericardial effusion is one critical condition to consider, despite it being an uncommon presentation in late-onset SLE. Mild pericarditis in an SLE case can be treated with corticosteroid administration. Colchicine also has been found to reduce the risk of pericarditis recurrence. However, an atypical presentation from this case led to a slightly delayed treatment that escalated the morbidity and mortality risk. The patient had a sudden cardiac arrest and passed away 3 days after being treated.Fig. 1Initial electrocardiogram demonstrated left-axis deviation, low voltage QRS complex and T-wave inversion on lead V1–V3Fig. 2Chest radiograph showed left massive pleural effusionFig. 3Transthoracic echocardiogram displayed increased left ventricular filling pressure with diastolic dysfunction grade III, mild circumferential pericardial effusion with adjacent pleural effusionConclusionsAtypical presentation during late-onset SLE, mainly in the form of pericardial effusion even constrictive pericarditis, should be taken into a consideration since they are a scarce feature in SLE patients. Swift recognition and prompt treatment are important for the optimal outcome.

Gender differences in SLE: report from a cohort of 417 Caucasian patients

BackgroundSLE is an autoimmune disease that predominantly affects women. As most epidemiological and interventional studies are on populations with a clear female prevalence, the influence of gender in disease course,...

Late Onset Systemic Lupus Erythematosus: Different Clinical, Serological Presentations and Damage Compared to Adult Lupus in Egypt

Late Onset Systemic Lupus Erythematosus: Different Clinical, Serological Presentations and Damage Compared to Adult Lupus in Egypt

Case Report: Extensive digital gangrene as a primary manifestation of late-onset systemic lupus erythematosus

Background: Digital gangrene is a rare but serious complication of systemic lupus erythematosus (SLE). It occurs usually in middle-aged patients with longer disease duration. Case: Herein we report the case of a 56-year-old man (with no history suggestive of Raynaud’s phenomenon, diabetes mellitus, smoking, trauma, infection, or chemical exposure), who presented with SLE and digital gangrene was among the first signs. He presented with a one-month history of joint pain, hair loss, photosensitivity, mouth ulcers, malar rash, dyspnea, and digital pain. Physical examination revealed painful and diffuse erythematous skin lesions in the extremities and back, as well as cyanosis in the fingers. We noted lymphocytopenia (600 cells/mm3), and an elevated C-reactive protein (15.1 mg/l) on laboratory tests. Immunological tests were positive for antinuclear antibodies (ANA) with Title 1:400. Pulmonary computed tomography revealed pulmonary fibrosis, and pulmonary function tests revealed the restrictive pulmonary disease. Diagnosis of SLE with lung involvement was retained. The immunological assessment in search of elements in favor of a vascular origin of the patient's skin lesions was negative. Treatment was initiated with 200 mg/day hydroxychloroquine. For dermal and pulmonary involvement, intravenous (IV) pulse therapy was used with methylprednisolone (1,000 mg/d for three consecutive days monthly) and cyclophosphamide (1 g/month). Calcium blocking agents were also prescribed. However, the lesions did not improve. The patient was given two infusions of rituximab (1 g) at a 14-day interval with a marked improvement of the majority of vasculitis lesions, and a partial improvement of dyspnea. Conclusions: Digital gangrene is a rare complication of late-onset SLE, especially as a primary manifestation.

Clinical and laboratorial outcome of different age-onset systemic lupus erythematosus patients in Jiangsu, China: a multicentre retrospective study

Studies on clinical features of systemic lupus erythematosus among different age-onset patients are lacking in China. This multicentre study aimed to systemically compare clinical manifestations, comorbidities, organ involvement, and laboratory findings among 797 Chinese juvenile-onset, adult-onset, and late-onset SLE (JSLE, ASLE, and LSLE) patients. They were classified into JSLE, ASLE, and LSLE groups if first diagnosed at < 18, 18–50, and > 50 years old, respectively. Chi-square test and analysis of variance were employed for categorical and continuous variables respectively. In younger-onset patients, the SLE Disease Activity Index 2000 score was significantly higher (JSLE vs. ASLE vs. LSLE = 17.43 ± 9.139 vs. 16.34 ± 8.163 vs. 14.08 ± 6.474, p = 0.031). Mucocutaneous symptoms (79.5% vs. 73.4% vs. 62.0%, p = 0.042), especially malar rash (76.1% vs. 66.1% vs. 53.5%, p = 0.011) occurred more frequently, and proteinuria rate was higher (54.5% vs. 56.3% vs. 36.6%, p = 0.007). In later-onset patients, cardiopulmonary involvement increased (11.4% vs. 24.3% vs. 29.6%, p = 0.012). In ASLE, hypoalbuminemia rate elevated (46.6% vs. 59.9% vs. 47.9%, p = 0.015). Our study demonstrated in a Chinese population that JSLE may be more active and suffer mucocutaneous disorders, while LSLE tended to suffer cardiopulmonary involvement at-onset. These findings may help identify treatment priorities when facing different age-onset SLE patients.