SLICC Damage Index Research Articles

Fibromyalgia, mood disorders and chronic damage are the main determinants of worse quality of life in systemic lupus erythematosus patients: Results from a cross-sectional analysis.

As suggested by the EULAR recommendations, a comprehensive management of Systemic Lupus Erythematosus (SLE) should include the evaluation of disease activity, chronic damage, and quality of life (QoL). QoL is significantly impaired in SLE patients, even in those achieving a state of remission, suggesting the possible contribution of other factors. Thus, in the present study we aimed at analyzing QoL in a large SLE cohort by using LupusQoL, and at identifying the main determinant of poorer QoL. We conducted a cross-sectional study by including consecutive SLE patients diagnosed according to the 2019 ACR/EULAR criteria. Clinical, laboratory and therapeutical data were collected. Disease activity was assessed by SLEDAI-2k, while chronic damage by the SLICC Damage Index (SDI). The diagnosis of fibromyalgia was made in accordance with the ACR criteria (2016). At the time of the enrollment, all patients completed the following questionnaires: LupusQoL to assess quality of life and hospital anxiety and depression scale (HADS) for anxiety and depression. Our analysis included 237 SLE patients [92.4% female, median age 46years (IQR 19.5), median disease duration 156.8months (IQR 180.6)]. At the time of enrollment, we found a mean SLEDAI-2k of 1.7 (DS 2.4); 104 patients (43.9%) had chronic damage, with a mean SDI value of 0.8 (DS 1.3). Patients diagnosed with fibromyalgia were 69 (29.1%); moreover, HADS questionnaire identified a condition of anxiety and depression in 112 (47.3%) and 94 (39.7%) patients, respectively. The most compromised domain in the LupusQoL resulted "fatigue", followed by "burden to others". Patients with SDI ≥ 1 showed lower quality of life than patients without chronic damage, as demonstrated by significantly lower values in all items of the LupusQoL (p < .01). Furthermore, significantly lower values in all the LupusQoL domains were observed in patients with fibromyalgia, anxiety and depression, in comparison to those patients without these manifestations (p < .0001). No association was demonstrated between QoL and disease activity. Finally, the linear regression analysis confirmed mood disorders, in particular depression, and fibromyalgia as the main determinants of worse quality of life in our cohort. The present study demonstrated the influence of different factors in the quality of life of SLE patients. In particular, the presence of mood disorders, fibromyalgia and chronic damage resulted the main determinants of poorer QoL. This evidence reinforces the need for a comprehensive patient care.

Clinical Features and Survival Analysis of Lupus Nephritis among Patients with Systemic Lupus Erythematosus: A Three-Decade-Long Retrospective Cohort Study.

Background/Objectives: Lupus nephritis (LN) is one of the most severe organ manifestations of systemic lupus erythematosus (SLE). The aim of our retrospective cohort study was to compare the clinical characteristics, therapy, survival, causes of death, and prognostic factors of LN and non-LN lupus patients. Moreover, we compared a wide spectrum of clinical data of LN patients diagnosed before and since 2005 to determine any changes in disease course and outcomes. Methods: We assessed the clinical and laboratory data of 384 SLE patients, out of whom, 127 patients were diagnosed with LN between 1990 and 2020. Results: Based on our observations, discoid LE, subacute cutaneous LE, antiphospholipid syndrome, Sjögren's syndrome, and rheumatoid arthritis were more common in non-LN patients, while anemia and anti-RNP positivity were more frequent in LN patients. Development of LN did not affect survival rates; male sex and presence of APS were negative prognostic parameters in the non-LN group while achieving remission was a positive prognostic factor in both groups. Death caused by sepsis was more prevalent in the LN group. Serositis and neurological manifestations occurred less frequently in LN patients diagnosed after 2005. The use of mycophenolate mofetil became more common, and the cumulative corticosteroid dose decreased. The SLICC Damage Index score also decreased. Conclusions: Our study demonstrated that the disease course has changed in recent years, and the main therapeutic goal in both SLE and lupus nephritis should be to achieve remission because this significantly improves long-term prognosis and patient survival.

Long-term outcomes of childhood-onset systemic lupus erythematosus.

Data on the long-term outcome of patients with childhood-onset Systemic Lupus Erythematosus (cSLE) are scarce. Aims of this study were to describe the long-term outcomes of cSLE and to identify factors associated with the development of damage and persistent disease activity. We conducted a retrospective multicentre study using data from the PEDIALUP registry of the Juvenile Inflammatory Rheumatism (JIR) cohort database. Demographic characteristics, clinical manifestations, laboratory, radiological, histological and treatment data were collected from medical records during follow-up. A total of 138 patients with cSLE, diagnosed between 1971 and 2015, were included. With a median follow-up of 15.4 [9.6-22.4] years, 51% of patients had a SLICC-Damage Index score ≥ 1 at last follow-up with the musculoskeletal, cutaneous, renal, neurological, and cardiovascular damage being the most common manifestations. The proportion of patients with a SLICC-DI score ≥ 1 increased significantly with the duration of the follow-up (p< 0.001). On multivariate analysis, duration of follow-up was associated with increased risk of cumulative damage (OR 1.08, 95% CI 1.01, 1.15, p= 0.035). At the last visit, 34% of patients still had active disease with a SLEDAI score of ≥ 6. On multivariate analysis, Sub-Saharan African ethnicity was associated with 7-fold increased odds of having active disease at the last visit compared with Caucasians (OR 7.44, 95% CI 2.24, 24.74, p= 0.0002). The prevalence of damage remains high in patients with cSLE even when the diagnosis of c-SLE has been made in the recent decades.

Clinical Significance of Serum Cystatin C in SLE: A Potential Marker of Disease Damage Beyond Lupus Nephritis

Objective: This work aimed to assess the serum level of cystatin C in systemic lupus erythematosus (SLE) patients and to determine the relation to disease characteristics and damage. Methods: The study included 33 SLE patients presenting to the Internal Medicine and Rheumatology Department and Outpatient clinic, King Abdulaziz University, Saudi Arabia. The medical history, clinical examination, laboratory investigations and medications received by the patients were recorded. The systemic lupus international collaborating clinics damage index (SLICC-DI) was assessed. Serum cystatin C was measured using the immune-nephelometric method. Results: The mean age of the patients was 35.3±10.7 years; 28 females and 5 males (F:M 5.6:1), disease duration 5.5±3.1 years and their age at onset was 27.9±10.6 years. Serum cystatin C level was significantly higher in patients with lupus nephritis (LN) (2.47±1.57 mg/L vs v mg/L, p=0.003) and diabetes (4.92±0.05 mg/L vs 1.93±1.34 mg/L; p&lt;0.0001) and was lower in those with thyroid dysfunction (1.41±0.75 mg/L vs 2.3±1.59 mg/L, p=0.047). There was a significant correlation between the serum cystatin C level with proteinuria (r=0.57, p=0.011) and with the SLICC-DI (r=0.42,p=0.016). Serum cystatin C could discriminate patients with LN at cut-off value of 0.904 mg/L with area under the curve of 0.765, sensitivity 87% and specificity 50%; p=0.017. Conclusion: The remarkable association between cystatin C and LN is confirmed and an emerging role is noted in reflecting the extent of disease damage. The likely association with diabetes and thyroid dysfunction should also be taken into consideration when deciding treatment regimens for LN patients.

Gender-driven thyroid dysfunction in systemic lupus erythematosus patients: Clinical significance of an overlooked association and global stance

Aim of the workThis study aimed to determine the association of thyroid dysfunction in systemic lupus erythematosus (SLE) patients. Patients and methodsOut of a cohort including 312 adult SLE patients those with thyroid dysfunction (n = 53) were further evaluated. The medical history, clinical examination, laboratory investigations and medications received were recorded. The SLICC damage index (SLICC-DI) was assessed. ResultsThyroid dysfunction formed 17 % of the patients and their mean age was 39.5 ± 11.5 years and disease duration 5.6 ± 3.3 years were comparable to those without thyroid disorder, however female gender was predominantly higher (F:M 52:1 vs 6.2:1, p < 0.0001). The frequency of thyroid dysfunction was alike in Saudi (16 %) and non-Saudi (17.9 %) patients (p = 0.66). The majority of cases (96.2 %) had hypothyroidism, one with autoimmune thyroiditis, while only 2 (3.8 %) had hyperthyroidism. There was a significantly increased frequency of associated neuropsychiatric manifestations (64.2 % vs 45.2 %;p = 0.012), and hematological involvement (32.1 % vs 14.3 %; p = 0.011) and less complement (C4) consumption (15.1 % vs 23.6 %; p = 0.048) in those with thyroid dysfunction compared to those without. The frequency of anti-double stranded deoxyribonucleic acid (anti-dsDNA) positivity tended to be higher (71.7 % vs 66.8 %) and its titre significantly lower (316.3 ± 319.8 IU/ml vs 461.3 ± 459.1; p = 0.013). The SLICC-DI and mortality rate were comparable between groups. Only the presence of proteinuria inversely significantly correlated with the level of T4 (r = -0.31, p = 0.007). ConclusionThyroid dysfunction forms a notable percentage of SLE patients with a prominent female gender propensity. The significant relation of thyroid disorders to neuropsychiatric manifestations, hematological involvement, C4 consumption and anti-dsDNA deserves recognition.

First validation of the childhood lupus low disease activity state (cLLDAS) definition in a real-life longitudinal cSLE cohort

ObjectivesTo validate the childhood lupus low disease activity state (cLLDAS) definition in cSLE by describing differences in time to reach first adult LLDAS (aLLDAS) versus cLLDAS. Secondly, to analyse positive and negative predictors for maintaining cLLDAS for at least 50% of follow-up time (cLLDAS-50) and for the occurrence of damage. MethodsProspective longitudinal data from a cSLE cohort were analysed. Used definitions were: aLLDAS according to Franklyn, cLLDAS by cSLE treat-to-target (T2T) Task Force, disease activity score by SLEDAI -2 K and damage by SLICC damage index. ResultsFifty cSLE patients were studied, with a median follow-up of 3.1 years. Each patient reached aLLDAS and cLLDAS at least once. Mean time to reach first aLLDAS/cLLDAS was 8.2/9.0 months, respectively. For 22/42 patients the mean steroid-dose related delay to reach first cLLDAS was 6.2 months. 58% of patients were able to maintain cLLDAS-50. Time to first cLLDAS (OR 0.8, p = 0.013) and higher number of flares (OR 0.374, p = 0.03) were negative predictors to maintain cLLDAS-50. Damage occurred in 34% of patients (23.5% steroid-related), in 64.7% within one year after diagnosis. African/Afro-Caribbean ethnicity, neuropsychiatric involvement and ever use of a biologic were significant predictors for damage. ConclusionTime to reach cLLDAS in cSLE differs from time to (a)LLDAS, which validates the new cLLDAS definition. Attaining cLLDAS-50 was difficult in real-life. This cohort shows the high risk for early damage in cSLE. T2T with earlier focus on steroid-tapering and starting steroid-sparing drugs seems important to prevent (steroid-related) damage in cSLE.

Glucocorticoid toxicity index in patients with systemic lupus erythematosus (preliminary data)

Objective: to investigate the contribution of glucocorticoids (GC) to the development of irreversible organ damage in patients with systemic lupus erythematosus (SLE) using the GC toxicity index (GTI).Material and methods. The study included 65 patients with SLE who met the 2012 SLICC classification criteria. GTI, disease activity according to the SLEDAI-2K index and the SLICC damage index (DI) were determined in all patients, and standard laboratory and immunological tests were performed.Results and discussion. Patients were predominantly female (n=56, 86%), median disease duration was 76 [2; 288] months, SLEDAI-2K – 8.8 [0; 26], DI SLICC – 1.0 [0; 5], DI SLICC &gt;0 was found in 28 (43%) patients. The median duration of GC therapy during the disease period was 66.0 [0; 288] months, maximum dose of GC – 32.7 [0; 80] mg, median of total GC dose during intravenous administration was 2942 [0; 17 812.5] mg, GTI at the time of enrolment in the study – 19 [0; 37] points. GTI &gt;0 was present in 47 (72%) of 65 patients. GTI correlated with disease duration (r=0.33; p&lt;0.008); maximum dose of oral GCs (r=0.31; p&gt;&lt;0.012); duration of GC use (r=0.35; p&gt;&lt;0.005); DI SLICC (r=-0.43; p&gt;&lt;0.0001). In patients with an average disease duration of more than 3 years, GTI&gt;˂0.008); maximum dose of oral GCs (r=0.31; p˂0.012); duration of GC use (r=0.35; p˂0.005); DI SLICC (r=-0.43; p˂0.0001). In patients with an average disease duration of more than 3 years, GTI was significantly higher than in patients with a disease duration of 1–3 years (p=0.023).Conclusion. An GTI&gt;0 was found in 72% of SLE patients, which increased significantly with disease duration. The GTI value was influenced by the duration of SLE, the duration of GC treatment and the maximum GC dose during the disease period. A statistically significant correlation was found between the GTI and the SLICC DI, allowing the GTI value to be used as an additional component in the assessment of the contribution of GCs to the development of irreversible organ damage in patients with SLE. It is recommended that GTI is assessed in all patients with SLE receiving long-term GC treatment for the purpose of dose adjustment.

Clinical Characteristics of Pre-pubescent Patients with Systemic Lupus Erythematosus (SLE)

Background: Systemic Lupus Erythematosus (SLE) is a chronic autoimmune condition that affects multiple organ systems, including cutaneous, renal, neurological, and hematological disorders. Pediatric SLE (pSLE) has a prevalence of 3.3-8.8 cases per 100,000 children. Children with SLE (cSLE) have higher disease severity than adults, but the evidence on cSLE is mostly from pubertal patients, and the reasons for the variation on presentation is unclear. There is limited data on prepubertal SLE, as SLE rarely affects pre-pubescent patients. This study aims to outline the clinical characteristics, disease activity and organ damage of pre-pubescent patients with SLE. Methods: A retrospective study was performed on prospectively collected multi-center data from 2005-2015. Patient data, including race, ethnicity, sex, age of presentation and diagnosis, Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) score, and Systemic Lupus International Collaborating Clinics (SLICC) damage index was collected using REDcap. Results: This study included 43 pre-pubescent SLE patients, with an average age at diagnosis of 9.7 years and 10.7 years at the study's start. Organ systems with the highest prevalence rates were musculoskeletal (Arthritis – 69.77%) and cutaneous (Malar rash – 58.14%). The organ systems with the highest involvement frequency, according to the SLICC damage index, were skin (alopecia - 9.3%), ocular (retinal changes/optic atrophy/cataracts - 9.3%), gastrointestinal (pancreatic insufficiency – 4.65%), neuropsychiatric (cognitive impairment – 4.65%), and renal (reduced glomerular filtration rate – 4.65%). Throughout the study, all patients had SLEDAI scores ranging from no activity to high activity, with 55.8% having mild activity, 27.9% having moderate activity, and 14% having high activity. Conclusion: Similar to SLE studies on pediatric populations, our study found that cutaneous, gastrointestinal, and renal manifestations were common. However, we found a high prevalence of damage in prepubertal patients, in particular ocular and cognitive impairment. This highlights the need to prioritize ocular exams and cognitive assessments in patients with prepubertal SLE.

Clinical Characteristics of Systemic Lupus Erythematosus in Caucasians and Latin American Hispanics: Data from a Single Tertiary Center.

Different studies report that systemic lupus erythematosus (SLE) tends to have a more aggressive course in Hispanic patients. In this study, we analysed epidemiologic, clinical, and laboratory characteristics in a cohort of Hispanic and Caucasian lupus patients in the context of Italian health service, which provides free access to care to all citizens, thus mitigating the impact of socioeconomic factors that negatively influence the course of the disease in ethnic minorities. This single-center retrospective study was conducted at the San Martino Hospital "Lupus Clinic" in Genoa, Italy. Patients ≥18 years with a confirmed diagnosis of SLE and definite ethnicity (Hispanic or Caucasian) were recruited. A total of 126 patients (90 Caucasians and 36 Hispanics) were enrolled. We compared epidemiologic characteristics, clinical features, autoantibodies profile, and treatment options without evidencing any statistically significant difference between the two groups, except for disease duration, which was higher in the Caucasian group (20.4 years versus 14.2 years in the Hispanic group, P=0.002) and SLICC damage index, which was greater in Caucasian patients (2.11 versus 1.88 in Hispanics, P=0.037), but this difference was no longer significant after correction for disease duration (P=0.096). In our cohort, Hispanic ethnicity is not associated with worse disease features and outcomes. Therefore, we speculated that socioeconomic factors, in particular, free access to healthcare, might be more relevant in influencing the course of the disease than genetic background.

N-terminal pro-brain natriuretic peptide is a biomarker for cardiovascular damage in systemic lupus erythematous: a cross-sectional study.

Prediction models based on traditional risk factors underestimate cardiovascular (CV) risk in systemic lupus erythematosus (SLE). In a large sample of unselected SLE patients, we investigated cross-sectional associations of NT-proBNP with cardiovascular damage (CVD). Serum NT-proBNP was measured in SLE patients enrolled in the MUHC Lupus Clinic registry. Serum was collected between March 2022 and April 2023 at annual research visits. The primary outcome was CVD identified on the SLICC Damage Index. Factors associated with CVD and NT-proBNP levels were determined. Overall, 270 SLE patients [female 91%, median age 50.7 (first quartile to third quartile: 39.6-62.1) years] were analysed for the primary outcome. Among them, 33 (12%) had CVD. The ROC curve for NT-proBNP demonstrated strong associations with CVD (AUC 0.78, 95% CI 0.69-0.87) with a threshold of 133 pg/ml providing the best discrimination for those with/without CVD. Hypertension (OR 3.3, 95% CI 1.2-9.0), dyslipidaemia (OR 3.6, 95% CI 1.3-9.6) and NT-proBNP >133 pg/ml (OR 7.0, 95% CI, 2.6-19.1) were associated with CVD in the multivariable logistic regression model. Increased NT-proBNP levels were associated with age (OR 4.2, 95% CI 2.2-8.3), ever smoking (OR 1.9, 95% CI 1.0-3.5), reduced eGFR (4.1, 95% CI 1.3-13.1), prior pericarditis/pleuritis (OR 2.5, 95% CI 1.4-4.5) and aPL antibodies (OR 2.6, 95% CI 1.4-4.9). NT-proBNP is a biomarker for CV damage in SLE. The novel associations of NT-proBNP levels with prior pericarditis/pleuritis and aPL antibodies suggest new avenues for research to better understand what drives CV risk in SLE.

Subtherapeutic hydroxychloroquine concentration is associated with increased disease activity and greater organ damage in lupus.

To investigate the effects of the serum HCQ concentration on clinical manifestations, disease activity and organ damage in a longitudinal cohort of SLE patients. The 338 SLE patients were assessed with respect to their demographic data, clinical and laboratory findings, Physician's Global Assessment (PGA), adjusted mean SLEDAI-2000 (AMS) and SLICC Damage Index (SDI) annually for 5 consecutive years. Patients were divided into two groups according to their serum HCQ concentration at baseline: subtherapeutic (<500 ng/ml) and therapeutic (≥500 ng/ml) groups. The impact of the HCQ concentration on the clinical outcomes was evaluated in a longitudinal analysis using a generalized estimating equation (GEE). Of the 338 patients, 287 (84.9%) were in the subtherapeutic group at baseline. This group had a higher incidence of newly developed LN (P = 0.036) and had been prescribed higher mean and cumulative doses of prednisolone (P = 0.003 and P = 0.013, respectively) than the therapeutic group. In multivariable analyses based on GEE, the subtherapeutic group had a higher AMS score (β = 1.398, 95% CI 0.607, 2.189; P < 0.001), higher PGA score (β = 0.328, 95% CI 0.215, 0.441; P < 0.001) and higher SDI score (β = 0.366, 95% CI 0.061, 0.671; P = 0.019) across all 5 years. The subtherapeutic HCQ concentration was associated with the development of new-onset LN, and had significant associations with disease activity and cumulative organ damage in SLE patients over time.

Assessment of cutaneous disease activity in early lupus and its correlation with quality of life: a cross-sectional study.

Systemic lupus erythematosus (SLE) is a multi-system autoimmune disease with varied dermatological manifestations that are almost universal. Overall, lupus disease has a major effect on the quality of life in these patients. We assessed the extent of cutaneous disease in early lupus and correlated it with the SLE quality-of-life (SLEQoL) index and disease activity measures. Patients diagnosed as SLE with the skin involved were recruited at the first presentation and were assessed for cutaneous and systemic disease activity using the cutaneous lupus erythematosus disease area and severity index (CLASI) and the Mexican-SLE disease activity index (Mex-SLEDAI), respectively. Quality of life was assessed with the SLEQoL tool while systemic damage was captured by the SLICC damage index. Fifty-two patients with SLE who had cutaneous involvement were enrolled (40, 76.9% females) with a median disease duration of 1month (1-3.7). The median age was 27.5years (IQR: 20-41). Median Mex-SLEDAI and SLICC damage index were 8(IQR: 4.5-11) and 0 (0-1), respectively. The median CLASI activity and damage scores were 3 (1-5) and 1 (0-1), respectively. Overall, there was no correlation between SLEQoL with CLASI or CLASI damage. Only the self-image domain of SLEQoL correlated with total CLASI (ρ = 0.32; p = 0.01) and CLASI-D (ρ = 0.35; p = 0.02). There was a weak correlation of CLASI with the Mexican-SLEDAI score (ρ = 0.30; p = 0.03) but not with the SLICC damage index. In this cohort of early lupus, cutaneous disease activity in lupus had a weak correlation with systemic disease. Cutaneous features did not appear to influence the quality of life except in the self-image domain.

Validation and the associated factors of the Malay version of systemic lupus erythematosus-specific health-related quality of life questionnaires (SLEQoL and LupusQoL).

To assess the reliability and validity of two disease-specific questionnaires that assess the quality of life (QoL) among patients with Systemic Lupus Erythematosus (SLE); SLEQoL and LupusQoL in Malay language. This study also identified the factors affecting each domain of the questionnaires. This cross-sectional study was conducted from June 2021 until April 2022, and SLE patients were recruited to complete the SLEQoL, LupusQoL and Short Form Health Survey (SF-36) in Malay language. Disease activity were recorded using the modified SLE Disease Activity Index (M- SLEDAI) and British Isles Lupus Assessment Group 2004 (BILAG-2004) index. Presence of organ damage was determined using the SLICC Damage index. Cronbach's alpha was calculated to determine internal consistency while exploratory factor analysis was done to determine the construct validity. Concurrent validity was evaluated using correlation with SF-36. Multiple linear regression analysis was deployed to determine the factors affecting each domain of SLEQoL and LupusQoL. A total of 125 subjects were recruited. The Cronbach's α value for the Malay-SLEQoL (M-SLEQoL) and Malay-LupusQOL (M-LupusQoL) was 0.890 and 0.944 respectively. Exploratory factor analysis found formation of similar number of components with the original version of questionnaires and all items have good factor loading of >0.4. Both instruments also had good concurrent validity with SF-36. M-SLEQoL had good correlations with BILAG-2004 and M-SLEDAI scores. Musculoskeletal (MSK) involvement was independently associated with lower M-SLEQoL in physical function, activity and symptom domains. Meanwhile, MSK and NPSLE were associated with fatigue in M-LupusQoL. Both M-SLEQoL and M-LupusQoL are reliable and valid as disease -specific QoL instruments for Malaysian patients. The M-Lupus QoL has better discriminative validity compared to the M-SLEQoL. SLE patients with MSK involvement are at risk of poor QoL in multiple domains including physical function, activity, symptoms and fatigue.

Tuberculosis remains a leading contributor to morbidity due to serious infections in Indian patients of SLE.

Infections are a major cause of morbidity and mortality in systemic lupus erythematosus (SLE). We assessed the incidence and risk factors for major infections in SLE in India. A retrospective review of a cohort of 1354 patients of adult SLE (ACR 1997 criteria) seen between 2000 and 2021 at a single center was conducted. Serious infections (need for hospitalisation, prolonged intravenous antibiotics, disability, or death) were recorded. Cox regression was used to determine factors associated with serious infection and the effects of serious infection on survival and damage. Among the 1354 patients (1258 females, mean age of 30.3years, follow-up of 7127.89 person-years), there were 439 serious infections in 339 patients (61.6 per 1000 person-years follow-up). Bacterial infections (N = 226) were the most common infection followed by mycobacterial infections (n = 81), viral (n = 35), and then invasive fungal infections (N = 13). Mycobacterium tuberculosis was the single most common microbiologically confirmed organism with incidence of 1136.4/100,000 person-years with 72.8% of them being extrapulmonary. Infection free survival at 1year and 5years was 82.9% and 73.8%. There were 119 deaths with infection attributable mortality in 65 (54.6%). On multivariable Cox regression analysis, higher baseline activity (HR 1.02, 1.01-1.05), gastrointestinal involvement (HR 2.75, 1.65-4.69), current steroid dose (HR 1.65, 1.55-1.76), and average cumulative steroid dose per year (HR 1.007, 1.005-1.009) were associated with serious infection and higher albumin (HR 0.65, 0.56-0.76) was protective. Serious infections led to greater damage accrual (median SLICC damage index of 1 vs. 0) and mortality (HR was 18.2, 32.7 and 81.6 for the first, second, and third infections). Serious infections remain a major cause of mortality and damage accrual in SLE and higher disease activity, gastrointestinal involvement, hypoalbuminemia, current steroid dose, and cumulative steroid dose are the risk factors for it.

Clinical significance of peripheral nervous system involvement in systemic lupus erythematosus patients: Relation to disease activity and damage index

BackgroundDespite its potential impact on disease outcome, peripheral nervous (PN) system involvement in systemic lupus erythematosus (SLE) has received little attention. Aim of the workTo assess the frequency and clinical features of PN system involvement in SLE patients. Patients and methodsThe medical records of 100 patients were revised. Cases with diabetes, hepatitis, vitamin B12 deficiency or carpal tunnel syndrome were excluded. Detailed history, clinical examination and laboratory investigations were recorded. PN events were documented. The SLE disease activity index (SLEDAI) and systemic lupus international collaborating clinics damage index (SLICC-DI) were evaluated. ResultsPatients were 88 females and 12 males (F:M 7.3:1), mean age was 34.2 ± 8.3 years and disease duration 12.7 ± 5.4 years. The frequency of PN system involvement was 8 %; polyneuropathy (n = 5), mononeuritis multiplex (n = 2) and Guillain-Barré syndrome (n = 1). PN was associated with a significantly higher frequency of musculoskeletal (100 %), neuropsychiatric (100 %), pulmonary (62.5 %) and cardiovascular (37.5 %) manifestations as well as Raynaud's phenomenon (37.5 %) and secondary vasculitis (50 %) compared to those without (56.5 %,7.6 %,26.1 %,7.6 %,7.6 % and 12 %;p = 0.02,p < 0.001,p = 0.04,p = 0.03,p = 0.03,p = 0.017 respectively).anti-nuclear antibodies (87.5 % vs 92.4 %) and anti-double stranded DNA (71.4 % vs 69.6 %) positivity were comparable (p > 0.05). SLEDAI and SLICC-DI were significantly increased in patients with PN (26.5 ± 6.36 and 3.75 ± 0.98) compared to those without (11.5 ± 4.76 and 0.61 ± 0.56;p < 0.001 each). ConclusionSLE patients with PN involvement had a higher frequency of musculoskeletal, neuropsychiatric, pulmonary and cardiovascular manifestations in addition to Raynaud's and vasculitis. There is a potential association with disease activity and damage. Careful neurological assessment should be included in the workup of SLE patients.

Lupus nephritis as a specific clinical and immunological phenotype of systemic lupus erythematosus

Lupus nephritis (LN) is the leading cause of death in systemic lupus erythematosus (SLE), so its early detection and treatment is of utmost importance. Features of the onset, clinical signs, certain morphological classes, as well as more aggressive therapy make it possible to assign SLE with LN to a distinct disease phenotype.Objective: to characterize the clinical, immunological and morphological features of the SLE phenotype with a predominant kidney involvement based on a comparative analysis of patients with LN and without LN.Patients and methods. The study included 400 patients with SLE who met the 2012 SLICC criteria and were hospitalized to V.A. Nasonova Research Institute of Rheumatology from 2013 to 2021. The diagnosis of LN was established in 192 (48%) patients, of which in 82 (43%) it was confirmed by pathological study of kidney biopsy specimens (the SLE group with LN). In 208 (52%) patients, no kidney damage was observed, and they constituted the SLE group without LN.All patients underwent a standard examination with an assessment of disease activity according to the SLEDAI-2K index, irreversible changes in organs according to the SLICC damage index, immunological disorders, clinical and biochemical blood tests, urinalysis according to unified methods, glomerular filtration rate, as well as pathological examination of kidney biopsy specimens for confirmation of LN in the presence of an appropriate clinical picture. In patients of both groups, a comparative study of the main clinical, laboratory, immunological manifestations of SLE, the features of the disease onset, its first clinical signs, possible trigger factors, and the drugs used was carried out.Results and discussion. In the LN group, insolation was more likely to trigger the development of SLE than in the group without LN (respectively, in 26% and 13% of cases; p=0.007). In turn, SLE without kidney damage more often than SLE with LN debuted during pregnancy or after childbirth.The first signs of the disease in almost 40% of patients with LN were proteinuria and/or changes in urinary sediment, edema, increased blood pressure, the development of LN in some cases was preceded by polyarthritis or combined lesions of the skin and joints, but no later than 6 months, signs of kidney damage appeared. In the SLE group without LN, polyarthritis (in 33%), combined lesions of the skin and joints (in 26%), and Raynaud's syndrome (in 16%; p &lt;0.0001) were more often observed at the onset. In patients with LN, erythematous lesions of the facial skin ("butterfly", in 42%), serositis (exudative pleuritis — in 44%, pericarditis — in 46%, ascites and hydrothorax — in 5%; p&lt;0.0001), as well as hematological disorders such as anemia (in 63%), leukopenia (in 49%) and thrombocytopenia (in 42%) were present more frequently. With the development of LN, an acute course and high activity of the disease occurred significantly more often. In the study of immunological parameters in the group without LN, lupus anticoagulant (in 6%) and antibodies to SS-A/Ro and SS-B/La (in 18 and 9% of patients, respectively) were detected significantly more often, while in the LN group — hypocomplementemia (in 81%; p&lt;0.0001). Therapy also differed significantly: patients with LN received higher doses of glucocorticoids (p&lt;0.0001), mycophenolate mofetil, and cyclophosphamide.Conclusion. SLE with LN can be considered a distinct disease phenotype with a set of characteristics (clinical and laboratory parameters, response to therapy, prognosis) that distinguish it from other SLE variants.

Cardiac involvement in a Spanish unicentric prospective cohort of patients with systemic lupus erythematosus.

Cardiac involvement is one of the most frequent manifestations of Systemic Lupus Erythematosus (SLE). Transthoracic echocardiogram (TTE) may be valuable for the early detection of cardiac abnormalities in SLE. Few studies analyze both TTE findings in SLE and the risk factors that predispose to different cardiac manifestations in a long follow-up cohort. We aimed to investigate cardiac involvement's prevalence, risk factors, and outcomes in a Spanish Lupus Clinic. Spanish single-center prospective study of cardiac involvement in SLE. Two hundred and one patients met the 2019 EULAR/ACR classification criteria, performed TTE, and were eligible for the study. Cardiac involvement was present in 43.8%. Patients with older age, hypertension, hyperlipidemia, higher body mass index, peripheral arterial disease, thrombosis, and major cardiovascular events had significantly more cardiac involvement. Neurological, hematological, and serosal involvement (pleuritis and/or pericarditis) were clinical risk factors for abnormal TTE. The combination of the four clinical variables (dyspnea, chest pain, cough, and/or syncope) was present in 40.9% of the patients with abnormal TTE in the follow-up and was superior to each of the manifestations separately. Troponin I (TnI) ≥ 0.2ng/mL and NTproBNP ≥ 300 pg/mL were excellent biomarkers with a good correlation with cardiac abnormalities. Anti-B2GP1 was the only autoantibody associated with cardiac involvement in our cohort. Presenting cardiac involvement was correlated with higher SLICC Damage Index and increased mortality risk in the 2-year follow-up period. Cardiac involvement in SLE is diverse, heterogeneous, and highly prevalent. Presenting a pathological TTE was associated with greater damage accrual and greater mortality. Based on our results, we consider that echocardiographic screening of patients with SLE is essential, especially those symptomatic and/or with risk factors, to diagnose and treat cardiac involvement earlier.

Retinal toxicity in a multinational inception cohort of patients with systemic lupus on hydroxychloroquine

ObjectiveTo evaluate hydroxychloroquine (HCQ)-related retinal toxicity in the Systemic Lupus International Collaborating Clinics (SLICC) inception cohort.MethodsData were collected at annual study visits between 1999 and 2019. We followed patients with...

Validation of the Modified Fatigue Impact Scale in patients with systemic lupus erythematosus.

Patients with systemic lupus erythematosus (SLE) experience significant fatigue, a debilitating symptom associated with reduced quality of life. There has not yet been agreed on a simple and reliable method for assessing fatigue in SLE. To investigate the internal consistency, test-retest reliability and construct validity (convergent and discriminant validity) of the Modified Fatigue Impact Scale (MFIS) in patients with SLE. The secondary objective was to investigate the contribution of disease activity and organ damage to fatigue. Fatigue was assessed using the MFIS in 61 patients with SLE. Internal consistency of MFIS was assessed with Cronbach's alpha (α) and Principal Component Analysis. Test-retest reliability was evaluated using the intraclass correlation coefficient (ICC). Construct validity was studied using Spearman's rank correlation (rs). Associations between MFIS and disease activity and organ damage were estimated with rs. Internal consistency of the MFIS was excellent with Cronbach's α = 0.97 (95% confidence interval (CI): 0.96-0.98) for the complete scale. Test-retest reliability was good with ICC = 0.89 (95% CI: 0.78-0.95, p < 0.001). Construct validity was confirmed by Spearman's correlation (VT-SF36: rs = -0.73, p < 0.001. MH-SF36: rs = 0.70, p < 0.001). No significant correlation was found between the MFIS and SLEDAI (rs = 0.03, p = 0.83). There was a moderate correlation between MFIS and SLICC Damage Index (rs = 0.43, p < 0.001). The present study found the MFIS to be a reliable and valid instrument for assessing fatigue in SLE. Further investigations are needed to clarify if an association between measured fatigue and disease components exists.

Serologic phenotypes distinguish systemic lupus erythematosus patients developing interstitial lung disease and/or myositis.

ObjectivesTo determine if serologic phenotypes could be identified in systemic lupus erythematosus patients developing interstitial lung disease (ILD) and/or myositis.MethodsAdult SLE patients (without myositis/ILD at baseline) had annual assessments and serum sampling between 2000 and 2017. New-onset ILD was identified using the SDI pulmonary fibrosis item. New-onset myositis was identified using the SLICC Damage Index muscle atrophy/weakness item, the SLEDAI-2K item for myositis, and annual creatinine kinase testing. Chart review confirmed ILD/myositis cases and randomly sampled SLE patients from baseline formed our sub-cohort (N = 72). Cases and sub-cohort were compared regarding myositis-related biomarkers at baseline and at a randomly selected follow-up between baseline and end of observation (date of ILD/myositis diagnosis or Dec. 31, 2017). Descriptive analyses and hazards ratios (HRs) were generated for ILD/myositis incidence, focusing on baseline serology and adjusting for sex, race/ethnicity, age at SLE diagnosis, and SLE duration.ResultsFourteen SLE patients developed ILD (N = 9), myositis (N = 3), and/or both (N = 2). Thirteen of those (92.9%) developing ILD/myositis had at least one biomarker at baseline, versus 47 (65.3%) SLE patients who never developed myositis/ILD. The most common biomarkers in myositis/ILD were KL-6, anti-Ro52, and anti-Ku. Baseline biomarkers tended to remain positive in follow-up. In multivariate Cox regressions, SLE patients had higher risk of developing myositis/ILD with elevated baseline KL-6 (adjusted hazard ratio 3.66; 95% confidence interval 1.01, 13.3). When updating biomarkers over time, we also saw correlations between anti-Smith and ILD/myositis.ConclusionsBaseline myositis-related biomarkers were highly associated with ILD/myositis incidence. This is the first identification of biomarker phenotypes with ILD/myositis risk in SLE.