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The Systemic Lupus International Collaborating Clinics (SLICC), American College of Rheumatology (ACR), and the Lupus Foundation of America are developing a revised systemic lupus erythematosus (SLE) damage index (the SLICC/ACR Damage Index [SDI]). Shifts in the concept of damage in SLE have occurred with new insights into disease manifestations, diagnostics, and therapy. We evaluated contemporary constructs in SLE damage to inform development of the revised SDI. We conducted a 3‐part qualitative study of international SLE experts. Facilitated small groups evaluated the construct underlying the concept of damage in SLE. A consensus meeting using nominal group technique was conducted to achieve agreement on aspects of the conceptual framework and scope of the revised damage index. The framework was finally reviewed and agreed upon by the entire group. Fifty participants from 13 countries were included. The 8 thematic clusters underlying the construct of SLE damage were purpose, items, weighting, reversibility, impact, time frame, attribution, and perspective. The revised SDI will be a discriminative index to measure morbidity in SLE, independent of activity or impact on the patient, and should be related to mortality. The SDI is primarily intended for research purposes and should take a life‐course approach. Damage can occur before a diagnosis of SLE but should be attributable to SLE. Damage to an organ is irreversible, but the functional consequences on that organ may improve over time through physiological adaptation or treatment. We identified shifts in the paradigm of SLE damage and developed a unifying conceptual framework. These data form the groundwork for the next phases of SDI development.

Screening for cognitive impairment (CI) in systemic lupus erythematosus (SLE) relies on the American College of Rheumatology (ACR) neuropsychological battery (NB). By studying the concurrent criterion validity, our goal was to assess the Montreal Cognitive Assessment (MoCA) as a screening tool for CI compared to the ACR‐NB and to evaluate the added value of the MoCA to the Automated Neuropsychological Assessment Metrics (ANAM). A total of 285 adult SLE patients were administered the ACR‐NB, MoCA, and ANAM. For the ACR‐NB, patients were classified as having CI if there was a Z score of ≤–1.5 in ≥2 domains. The area under the curve (AUC) and sensitivities/specificities were determined. A discriminant function analysis was applied to assess the ability of the MoCA to differentiate between CI, undetermined CI, and non‐CI patients. CI was not accurately identified by the MoCA compared to the ACR‐NB (AUC of 0.66). Sensitivity and specificity were poor at 50% and 69%, respectively, for the cutoff of 26, and 80% and 45%, respectively, for the cutoff of 28. The MoCA had a low ability to identify CI status. The addition of the MoCA to the ANAM led to improvement on the AUC by only 2.5%. The MoCA does not have adequate concurrent criterion validity to accurately identify CI in patients with SLE. The low specificity of the MoCA may lead to overdiagnosis and concern among patients. Adding the MoCA to the ANAM does not substantially improve the accuracy of the ANAM. These results do not support using the MoCA as a screening tool for CI in patients with SLE.

To investigate the incidence of and factors associated with SARS–CoV‐2 testing and infection in immune‐mediated inflammatory disease (IMID) patients versus matched non‐IMID comparators from the general population. We conducted a population‐based, matched cohort study among adult residents from Ontario, Canada, from January 2020 to December 2020. We created cohorts for the following IMIDs: rheumatoid arthritis (RA), psoriasis, psoriatic arthritis, ankylosing spondylitis, systemic autoimmune rheumatic diseases, multiple sclerosis (MS), iritis, inflammatory bowel disease (IBD), polymyalgia rheumatica, and vasculitis. Each patient was matched with 5 patients without IMIDs based on sociodemographic factors. We estimated the incidence of SARS–CoV‐2 testing and infection in IMID patients and non‐IMID patients. Multivariable logistic regressions assessed odds of SARS–CoV‐2 infection. We studied 493,499 patients with IMIDs and 2,466,946 patients without IMIDs. Patients with IMIDs were more likely to have at least 1 SARS–CoV‐2 test versus patients without IMIDs (27.4% versus 22.7%), but the proportion testing positive for SARS–CoV‐2 was identical (0.9% in both groups). Overall, IMID patients had 20% higher odds of being tested for SARS–CoV‐2 (odds ratio 1.20 [95% confidence interval 1.19–1.21]). The odds of SARS–CoV‐2 infection varied across IMID groups but was not significantly elevated for most IMID groups compared with non‐IMID comparators. The odds of SARS–CoV‐2 infection was lower in IBD and MS and marginally higher in RA and iritis. Patients across all IMIDs were more likely to be tested for SARS–CoV‐2 versus those without IMIDs. The risk of SARS–CoV‐2 infection varied across disease subgroups.

ObjectiveTo evaluate whether a change in the European Alliance of Associations for Rheumatology (EULAR)/American College of Rheumatology (ACR) systemic lupus erythematosus (SLE) classification criteria threshold score affects accurate classification of SLE cases compared to disease-based control subjects. We evaluated a range of threshold scores to determine the score that maximizes the accurate classification of early SLE.MethodsWe conducted a cross-sectional study comparing SLE cases and control patients. A EULAR/ACR criteria score was calculated using baseline information. Sensitivity, specificity, positive likelihood ratios (+LRs), and negative likelihood ratios (−LRs) with 95% CIs were used to evaluate operating characteristics. Threshold scores of 6 to 12 were evaluated in subjects with early disease (ie, disease duration of ≤ 5 years). +LRs > 10 and −LRs < 0.1 provide evidence to rule in or rule out SLE.ResultsA total of 2764 patients were included: 1980 SLE cases who fulfilled either the ACR or Systemic Lupus International Collaborating Clinics criteria and 784 control subjects. The EULAR/ACR SLE criteria had a sensitivity of 98% (95% CI 97-98), a specificity of 99% (95% CI 98-100), a +LR of 95.5 (95% CI 48.0-190), and a −LR 0.03 (95% CI 0.02-0.03). The criteria operated well in those with early disease, in women, in men, and in White, Black, Chinese, and Filipino people. A score of 10 maximized the accurate classification of patients with early disease (+LR 174.4, 95% CI 43.8-694.6; −LR 0.03, 95% CI 0.02-0.04). An increase in the threshold score from 10 to 11 resulted in significant worsening in the −LR (threshold score 10: −LR 0.03, 95% CI 0.02-0.03 vs threshold score 11: −LR 0.05, 95% CI 0.04-0.06).ConclusionThe EULAR/ACR SLE classification criteria threshold score of 10 performs well, particularly among those with early disease and across sexes and ethnicities.

To identify discrete clusters of systemic lupus erythematosus (SLE) patients based on symptoms and investigate differences across clusters. Data were collected in the US and 5 European countries via the Adelphi Real World Lupus Disease Specific Programme, a cross‐sectional survey. Rheumatologists provided data for 5 consecutively consulting adult patients with SLE, who were invited to participate. Identified SLE symptoms were reduced to factors based on commonly concurrent symptoms, using principal‐component factor analysis. Factors were used as covariates in a latent‐class cluster analysis to identify discrete patient clusters. Patient‐reported outcomes and physician‐reported data were compared across clusters. Among 1,376 patients, 87% were female and 74% were White. We identified 4 patient clusters (very mild, mild, moderate, and severe) based on 39 signs/symptoms. Physician‐reported symptom burden, organ involvement, disease activity, and the number of flares increased with increasing cluster severity (P< 0.0001). Patient‐reported impact (health status, fatigue, work productivity impairment, anxiety/depression, and emotional impact) increased with increasing cluster severity (P< 0.0001). Glucocorticoid and immunosuppressant use increased, and antimalarial use decreased, with increasing cluster severity. In all clusters, <20% of patients received biologics; >15% of patients not receiving biologics were considered eligible for treatment by their physician. The proportion of physicians and patients satisfied with treatment decreased with increasing cluster severity (P< 0.0001). Our large, international, real‐world survey of SLE patients and physicians demonstrated strong associations between increased impairment, organ involvement, and humanistic burden in SLE, highlighting an unmet need for effective treatment options in patients with high disease activity.

ObjectiveTo investigate coronavirus disease 2019 (COVID-19) hospitalization risk in patients with immune-mediated inflammatory diseases (IMIDs) compared with matched non-IMID comparators from the general population.MethodsWe conducted a population-based, matched cohort study using health administrative data from January to July 2020 in Ontario, Canada. Cohorts for each of the following IMIDs were assembled: rheumatoid arthritis (RA), psoriasis, psoriatic arthritis (PsA), ankylosing spondylitis, systemic autoimmune rheumatic diseases (SARDs), multiple sclerosis (MS), iritis, inflammatory bowel disease, polymyalgia rheumatica, and vasculitis. Each patient was matched with 5 non-IMID comparators based on sociodemographic factors. We compared the cumulative incidence of hospitalizations for COVID-19 and their outcomes between IMID and non-IMID patients.ResultsA total of 493,499 patients with IMID (417 hospitalizations) and 2,466,946 non-IMID comparators (1519 hospitalizations) were assessed. The odds of being hospitalized for COVID-19 were significantly higher in patients with IMIDs compared with their matched non-IMID comparators (matched unadjusted odds ratio [OR] 1.37, adjusted OR 1.23). Significantly higher risk of hospitalizations was found in patients with iritis (OR 1.46), MS (OR 1.83), PsA (OR 2.20), RA (OR 1.42), SARDs (OR 1.47), and vasculitis (OR 2.07). COVID-19 hospitalizations were associated with older age, male sex, long-term care residence, multimorbidity, and lower income. The odds of complicated hospitalizations were 21% higher among all IMID vs matched non-IMID patients, but this association was attenuated after adjusting for demographic factors and comorbidities.ConclusionPatients with IMIDs were at higher risk of being hospitalized with COVID-19. This risk was explained in part by their comorbidities.

Cognitive function may change over time in patients with systemic lupus erythematosus (SLE), and cognitive function trajectories have not been well studied. We aimed to identify cognitive function trajectories in SLE and describe them with depressive symptoms trajectories, and we also aimed to identify baseline factors associated with class membership in the dual trajectories. Longitudinal data from the University of California San Francisco Lupus Outcomes Study were analyzed. Two outcome trajectories were studied jointly, the Hopkins Verbal Learning Test–Revised and the Center for Epidemiologic Studies Depression Scale (CES‐D) (administered annually). Univariate/multivariable logistic regression analyses examined baseline factors associated with class memberships. A total of 755 patients were studied, and 4 latent classes were identified: 1) low CES‐D scores and low cognitive scores (no depression plus cognitive impairment; 20%), 2) lowest CES‐D scores and highest normal cognitive scores (no depression plus normal cognition; 48%), 3) highest CES‐D scores and lowest cognitive scores (depression plus cognitive impairment; 9%), and 4) high CES‐D scores and cognitive score at borderline (depression plus borderline cognition; 23%). In all, 4 distinct classes of dual cognitive function and depressive symptoms were identified. Persistently low cognitive performance in 28% of patients (classes 1 and 3) did not significantly improve over 7 years. Cognitive impairment was associated with depression status in 9% of patients (class 3). Other factors also predicted latent class membership: ethnicity, education, disease activity, physical functioning, and bodily pain. These results highlight the importance of periodic assessment of cognitive function and of different aspects relevant for assessing and managing cognitive function over time in SLE.

To compare the performance of the Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI‐2K) and the SLEDAI‐2K Glucocorticoids (SLEDAI‐2KG) indices in identifying responders to standard of care therapy. Data from adult patients seen between 1995 and 2018 at the University of Toronto Lupus Clinic were analyzed. Patients with active disease (SLEDAI‐2K score ≥6) and receiving prednisone ≥5 mg/day, and with a follow‐up visit at 9 months, were studied. Response to standard of care therapy at first follow‐up visit was assessed using the SLEDAI‐2K and SLEDAI‐2KG. The performances of the SLEDAI‐2K and SLEDAI‐2KG were compared using a cutoff point of 4. In a cohort of 188, the majority of patients were female (86.0%) and White (47.9%). Of 188 patients, 145 (77.1%) were responders and had a decrease in SLEDAI‐2K score of ≥4. The SLEDAI‐2KG identified 142 (97.9%) responders among the SLEDAI‐2K responders. More importantly, the SLEDAI‐2KG identified 11 (25.6%) additional responders among SLEDAI‐2K nonresponders (n = 43). This resulted from the ability of the SLEDAI‐2KG to account for the decrease in glucocorticoids dose. The SLEDAI‐2KG provides a novel concept for the assessment of lupus disease activity while accounting for glucocorticoids dosage to reflect on disease activity overall at a particular visit. The SLEDAI‐2KG accounts for the disease activity for each descriptor while also accounting for the current glucocorticoids dosage. The SLEDAI‐2KG adds 1 additional variable (glucocorticoids dosage) to the SLEDAI‐2K, which could alter response rates in drug trials and observational studies.

Screening for cognitive impairment in systemic lupus erythematosus (SLE) conventionally relies on the American College of Rheumatology (ACR) neuropsychologic battery (NB), which is not universally available. To develop a more accessible screening approach, we assessed validity of the Automated Neuropsychological Assessment Metrics (ANAM). Using the ACR NB as the gold standard for cognitive impairment classification, the objectives were 1) to measure overall discriminative validity of the ANAM for cognitive impairment versus no cognitive impairment, 2) to identify ANAM subtests and scores that best differentiate patients with cognitive impairment from those with no cognitive impairment, and 3) to derive ANAM composite indices and cutoffs. A total of 211 consecutive adult patients, female and male, with SLE were administered the ANAM and ACR NB. 1) For overall discriminative validity of the ANAM, we compared patients with cognitive impairment versus those with no cognitive impairment on 4 scores. 2) Six ANAM models using different scores were developed, and the most discriminatory subtests were selected using logistic regression analyses. The area under the receiver operating characteristic curve (AUC) was calculated to establish ANAM validity against the ACR NB. 3) ANAM composite indices and cutoffs were derived for the best models, and sensitivities and specificities were calculated. Patients with no cognitive impairment performed better on most ANAM subtests, supporting ANAM’s discriminative validity. Cognitive impairment could be accurately identified by selected ANAM subtests with top models, demonstrating excellent AUCs of 81% and 84%. Derived composite indices and cutoffs demonstrated sensitivity of 78–80% and specificity of 70%. This study provides support for ANAM’s discriminative validity for cognitive impairment and utility for cognitive screening in adult SLE. Derived composite indices and cutoffs enhance clinical applicability.

A projectaimed at developingnew classification criteria for systemic lupus erythematosus (SLE) is based on weighted criteria that include both laboratory and clinical items. Combinations of certain symptoms may occur commonly in SLE, which provides an argument against independently counting these items. The current study was undertaken to evaluate the interrelationship between candidate criteria items in the International Early SLE cohort and in the Euro‐Lupus cohort. The International Early SLE cohort included 389 patients, who were diagnosed within 3 years prior to the study. Data on the ACR’s 1997 update of the SLE revised criteria, the Systemic Lupus International Collaborating Clinics 2012 criteria, and on 30 additional items were collected. To evaluate the interrelationship of the criteria, a tetrachoric correlation was used to assess the degree of association between different manifestations inthe same organ system. The correlations identified in the International Early SLE cohort were validated in the Euro‐Lupus cohort. A few relevant correlations were observed among specific clinical cutaneous manifestations (in particular, malar rash correlated with photosensitivity, alopecia, and oral ulcers) and serologic manifestations (anti‐Sm and anti–double‐stranded DNA and anti–RNA polymerase, anti‐Ro and anti‐La, and antiphospholipid antibodies), and these results were validated in the Euro‐Lupus cohort. The associations within the mucocutaneous domain, hematologic and the specific autoantibodies suggest that within a single domain only the highest ranking item should be counted to avoid overrepresentation. Some of the candidate SLE criteria cluster within domains. Given these interrelationships, multiple criteria within a domain should not be independently counted. These results are important to consider for the structure of new SLE classification criteria.

Introduction: The real-world effectiveness of belimumab for systemic lupus erythematosus (SLE) in six countries was evaluated in the OBSErve program. The aim of this post hoc analysis (GSK study 206351) was to pool individual patient OBSErve data to further evaluate the effectiveness of belimumab in a large sample of patients with SLE. Methods: OBSErve (Argentina, Canada, Germany, Spain, Switzerland, and the USA) enrolled adults?=?18 years of age with SLE, who were prescribed belimumab as part of standard therapy (index: date of belimumab initiation). Endpoints (month 6 vs. index) included physician-assessed overall clinical response to belimumab in the overall population (primary) and high disease activity subgroups (secondary; patients with a SLEDAI-2K/SELENA-SLEDAI score?=?10 or patients with high anti-dsDNA or low complement at index); other secondary endpoints included changes in glucocorticosteroid (GCS) use and changes in disease activity. Factors associated with physician-assessed overall clinical response were also evaluated. Results: In total, 830 patients were included in the overall population (mean [standard deviation (SD)] age: 41.9 [12.57] years; female: 89.3%; 60.4% from the USA). Nearly half (48.1%) of belimumab-treated patients experienced a?=?50% physician-assessed improvement in their overall manifestations, and 13% achieved a near normalization of their condition (equal to?=?80% improvement). Initiating belimumab while on high-dose (>?7.5 mg/day) GCS use was associated with?=?50% clinical improvement at month 6 (OR: 1.9, p?=?0.003). Most (78.1%; n?=?518/663) patients were able to reduce or discontinue their oral GCS dose after 6 months of belimumab, with a mean (SD) change of?-?8.5 (10.74) mg/day prednisone-equivalent. The mean (SD) change from belimumab initiation in disease activity score (SLEDAI-2K/SELENA-SLEDAI) was?-?5.7 (4.5; n?=?344). Conclusions: Belimumab improves clinical manifestations of SLE and is associated with GCS dose reductions in a real-world clinical setting, supporting the real-world effectiveness of belimumab for SLE.

The young age of onset and chronic/relapsing nature of systemic lupus erythematosus (SLE) make SLE patients prone to develop and accrue organ damage as a result of long-standing disease activity and side effects of treatment. There is a growing interest in objectifying damage and identifying its risk factors. Still, the lack of therapeutic alternatives has led to difficulties in avoiding immunosuppressives particularly corticosteroids, which have been implicated in a large spectrum of organ damage in SLE patients. Moreover, it continues to be very challenging to determine what actually causes damage in different organ-systems.

Background: Elevated levels of interferons (IFNs) are a characteristic feature of systemic autoimmune rheumatic diseases (SARDs) and may be useful in predicting impending symptomatic progression in anti-nuclear antibody-positive (ANA+) individuals lacking a SARD diagnosis. Typically, these are measured by their effect on gene expression in the blood, which has limited their utility in clinical settings. Here, we assessed whether the measurement of serum IFN-α or selected IFN-induced cytokines accurately mirrors IFN-induced gene expression in ANA+individuals and investigated their utility as biomarkers of clinical progression. Methods: A total of 280 subjects were studied, including 50 ANA−healthy controls, 160 ANA+individuals without a SARD diagnosis (96 asymptomatic, 64 with undifferentiated connective tissue disease), and 70 SARD patients. IFN-induced gene expression was measured by nanoString and cytokine levels by ELISA or Simoa. ANA+individuals lacking a SARD diagnosis who had the new onset of SARD criteria over the subsequent 2 years were defined as progressors. Results: Measurement of IFN-α levels by high-sensitivity ELISA or Simoa correlated much better with IFN-induced gene expression than measurement of CXCL-10 or Galectin-9 levels. Despite this, high CXCL-10 and Galectin-9 levels were better predictors of subsequent progression in ANA+individuals than measures of IFN-α or IFN-induced gene expression with the optimal combination of predictive cytokines (CXCL-10 and IFN-α as measured by ELISA), resulting in a specificity and positive predictive value of 100%. Conclusion: Easily performed ELISA assays for CXCL-10 and IFN-α can be used to predict ANA+individuals at high risk of imminent symptomatic progression.

Systemic Lupus Erythematosus (SLE) is an autoimmune disease with diverse manifestations, from mild and sporadic to severe and life-threatening. SLE heterogeneity arises from various factors, including genetic, epigenetic, and immune niche-related features (Kaul et al., 2016; Jenks et al., 2018). However, the exact interactions and hierarchy between these features remain unclear. Recent studies have found somatic mutations in genes typically mutated in B-cell lymphomas, in subsets of B-cells that are associated with SLE pathogenesis (Piotrowski et al., 2015; Pullabhatla et al., 2018; Singh et al., 2020; Brown et al., 2022). These mutations may support B-cell clonal bursts, but direct information from clinical specimens on the impact of these mutations on B-cell lineages and their influence on SLE progression or malignant transformation is missing.

A recent study conducted by our clinical group demonstrated that low disease activity (LDA), defined as a clinical Systemic Lupus Erythematosus Disease Activity Index 2000 (SLEDAI‐2K) score ≤2, maintained for 12 months, confers the same risk for damage accrual as complete remission after 2 years. The aim of the present study was to assess the validity of these findings in the long term (10 years). Patients in the inception cohort of the Toronto Lupus Clinic, who had a minimum follow‐up of 10 years and no interval >18 months between consecutive visits, were included in the analysis. Prolonged clinical remission was defined based on a SLEDAI‐2K score of 0 (serology excluded), achieved within the first 5 years of enrollment and maintained for ≥10 years. Prolonged LDAwas defined as SLEDAI‐2K score ≤2 (serology excluded) with the same time frame restrictions. Of 267 patients, 27 (10.1%) achieved prolonged clinical remission and 48 (18%) attained prolonged LDA. There were no differences regarding demographic, clinical, and immunologic variables at any time. The mean prednisone dose at enrollment was higher in patients in whom remission was achieved, while patients with prolonged LDAwere taking antimalarials more frequently, both at enrollment and after the 10‐year time period. Cumulative damage and flare rate after 10 years, and mortality throughout follow‐up were comparable. SLEin patients in the prolonged LDAgroup was in complete remission for 76% of the follow‐up time. Prolonged clinical remission and LDAwere demonstrated in 10.1% and 18% of our patients, respectively, and comparable outcomes were demonstrated in the long term, rendering sustained LDAan acceptable treat‐to‐target outcome in SLE.

Objective.As part of the Group for Research and Assessment of Psoriasis and Psoriatic Arthritis (GRAPPA) ultrasound working group, we performed a systematic review of the literature to assess the evidence and knowledge gaps in scoring instruments of enthesitis in psoriatic arthritis (PsA).Methods.A systematic search of PubMed, EMBase, and Cochrane databases was performed. The search strategy was constructed to find original publications containing terms related to ultrasound, enthesitis, spondyloarthritis (SpA) or PsA. Data extraction focused on the properties of the sonographic enthesitis instruments used in each study following components of the Outcome Measures in Rheumatology (OMERACT) filter: feasibility, test-retest reliability, construct validity as related to clinical assessment of enthesitis, biomarkers of inflammation and imaging of enthesitis by other modalities, discriminative validity, and responsiveness to treatment.Results.Fifty-one of 310 identified manuscripts were included. Only 1 scoring instrument of enthesitis was specifically developed and validated in patients with PsA. Only 18 (35%) of the studies involved patients with PsA, while the remaining studies focused on SpA. In PsA, construct validity was assessed using biomarkers and clinical examination in 1 (2%) and 11 (21.5%) of the studies, respectively, whereas no studies used imaging for the same purpose. Only 2 (4%) of the studies assessed discriminative validity in PsA. Responsiveness to treatment was assessed in 7 studies, none of which included patients with PsA.Conclusion.Although sonographic enthesitis scoring instruments have been developed for SpA, only a few have been validated in PsA. None of them passed the OMERACT filter in patients with PsA. Additional research is required before endorsing a specific instrument for the assessment of enthesitis in patients with PsA.

Objective.To develop definitions for the assessment of magnetic resonance imaging (MRI) pathologies of the sacroiliac joints (SIJ) in juvenile idiopathic arthritis.Methods.An Outcome Measures in Rheumatology (OMERACT) consensus-driven methodology consisting of iterative surveys and focus group meetings within an international group of rheumatologists and radiologists.Results.Two domains, inflammation and structural, were identified. Definitions for bone marrow edema, joint space inflammation, capsulitis, and enthesitis were derived for joint inflammation; sclerosis, erosion, fatty lesion, and ankylosis were defined for assessing structural joint changes.Conclusion.Preliminary consensus-driven definitions for inflammation and structural elements have been derived, underpinning the ongoing development of the OMERACT Juvenile Arthritis MRI SIJ scoring system (OMERACT JAMRIS-SIJ).

Ustekinumab is a monoclonal antibody targeting interleukin (IL)-12 and IL-23 and is approved for the treatment of plaque psoriasis, psoriatic arthritis, and Crohn's disease. IL-12 and IL-23 have been implicated in systemic lupus erythematosus. We aimed to assess the efficacy and safety of ustekinumab for the treatment of systemic lupus erythematosus in patients with moderate-to-severe disease activity despite conventional treatment.

ABSTRACTIntroduction: Cutaneous lupus erythematosus (CLE) encompasses a spectrum of dermatologic manifestations which can occur with or without systemic lupus erythematosus (SLE). Treatment of CLE is challenging as the traditional treatments are off label and often fail and there is no drug specifically approved for CLE. The knowledge gained from the emerging trials on biologic therapy in SLE has provided insight into the utility of biologic therapy for CLE.Areas covered: An overview is provided on the biological agents studied for CLE discussing their immunological target, their efficacy in treating the various CLE manifestations and the outcome measures used.Expert opinion: There is a paucity of trials dedicated to the biologic treatment of CLE. Several of the described biological treatments’ efficacy suggests that different clinical phenotypes of CLE may require different immunological targeted therapies. Recently published and ongoing trials of SLE focusing on novel agents for CLE using the Cutaneous Lupus Area and Severity Index (CLASI) as the outcome measure have shown promising results. Further trials designed specifically to study the efficacy of biologic treatment in CLE subgroups with or without systemic involvement using specific metrics for assessing cutaneous involvement are needed and will aid in illuminating the role of biologic therapy in CLE.

The transcription factor AhR modulates immunity at multiple levels. Here we report that phagocytes exposed to apoptotic cells exhibited rapid activation of AhR, which drove production of the cytokine IL-10. Activation of AhR was dependent on interactions between apoptotic-cell DNA and the pattern-recognition receptor TLR9 that was required for the prevention of immune responses to DNA and histones in vivo. Moreover, disease progression in mouse systemic lupus erythematosus (SLE) correlated with strength of the AhR signal, and the disease course could be altered by modulation of AhR activity. Deletion of AhR in the myeloid lineage caused systemic autoimmunity in mice, and an enhanced AhR transcriptional signature correlated with disease in patients with SLE. Thus, AhR activity induced by apoptotic cell phagocytes maintains peripheral tolerance. McGaha and colleagues show that phagocytosis of apoptotic cells leads to activation of the transcription factor AhR and production of the cytokine IL-10 in phagocytes, in a manner dependent on the recognition of DNA.

Clinicians, researchers, and outcome stakeholders have the crucial, albeit difficult, task of quantifying when a person or group experiences important change or difference on any given outcome measure, often in response to a specific intervention. The minimal clinically important difference (MCID) provides this quantified value of change/difference for a measure. There are many methods for MCID derivation, which can result in multiple values for the same measure. Thus, it is important for potential users of MCID values to be aware of the nuances of MCID development and cautions for interpreting values. This review outlines MCID-related definitions, methods, and guidelines.

Objective.Disease course in systemic lupus erythematosus (SLE) is primarily relapsing-remitting. Long quiescent and chronically active patterns are less frequent. We recently described an atypical “monophasic” course in a small number of patients. The aim of the present study was to assess the prevalence and characteristics of such patients in a defined SLE cohort.Methods.The inception patients of the University of Toronto Lupus Clinic (enrolled within 18 mos of diagnosis) were investigated. No time interval > 18 months was allowed between consecutive visits. A monophasic course was defined as Systemic Lupus Erythematosus Disease Activity Index 2000 = 0 (serology excluded), achieved within 5 years since enrollment and maintained for ≥ 10 years. Descriptive statistics were used.Results.Of 267 inception patients, 27 (10.1%) achieved prolonged clinical remission (≥ 10 yrs) and 20 (7.5%) sustained remission for the entire followup (18 yrs on average). Twelve patients were receiving no maintenance treatment 10 years after achieving remission. Clinical manifestations at diagnosis (apart from skin and musculoskeletal involvement) included 25% in each of central nervous system involvement and lupus nephritis (LN). Half the patients were serologically active. Ten years after achieving remission, two-thirds of the patients had discontinued glucocorticosteroids; the remaining were treated with 5 mg/day on average. Seven patients relapsed after 10 years, 4 with arthritis, 2 LN, and 1 catastrophic antiphospholipid syndrome.Conclusion.A monophasic disease course was observed in 7.5% in this inception cohort. Patients sustained remission for 18 years on average, eventually without medications. Further study of such patients may provide unique pathophysiologic insights for SLE.

Objective.To identify the effect of disease activity and damage, measured by validated indices, on mortality and damage accrual, in order to inform upcoming Canadian systemic lupus erythematosus (SLE) recommendations.Methods.Following GRADE (Grading of Recommendations Assessment, Development and Evaluation) methodology to fill in evidence-to-decision tables to create recommendations for “minimal investigations needed to monitor SLE patients at baseline and subsequent visits,” a systematic literature review was performed. The effect of disease activity and damage, measured by validated metrics, on mortality and damage was systematically reviewed, with metaanalyses performed when available.Results.A title/abstract screen of 5599 articles identified 816 articles for full paper review, with 102 meeting inclusion criteria and 53 with extractable data. Thirty-three articles describing outcomes related to disease activity and 20 articles related to damage were identified. Mortality was associated with higher SLE Disease Activity Index-2000 scores in 6 studies (HR 1.14, 95% CI 1.06–1.22) and higher Systemic Lupus International Collaborating Clinics/ACR Damage Index scores in 6 studies (HR 1.53, 95% CI 1.28–1.83). Higher SLE Activity Measure scores were associated with increased risk of damage in 3 studies (OR 1.06, 95% CI 1.04–1.08). British Isles Lupus Assessment Group was associated with mortality in 1 study with HR of 1.15.Conclusion.Active SLE disease and damage are associated with and predict greater mortality and damage. The use of validated disease activity and damage metrics is important in the assessment of disease activity and damage and will inform upcoming Canadian recommendations for the assessment of SLE.

Objective.To develop recommendations for the assessment of people with systemic lupus erythematosus (SLE) in Canada.Methods.Recommendations were developed using the GRADE (Grading of Recommendations Assessment, Development, and Evaluation) approach. The Canadian SLE Working Group (panel of Canadian rheumatologists and a patient representative from Canadian Arthritis Patient Alliance) was created. Questions for recommendation development were identified based on the results of a previous survey of SLE practice patterns of members of the Canadian Rheumatology Association. Systematic literature reviews of randomized trials and observational studies were conducted. Evidence to Decision tables were prepared and presented to the panel at 2 face-to-face meetings and online.Results.There are 15 recommendations for assessing and monitoring SLE, with varying applicability to adult and pediatric patients. Three recommendations focus on diagnosis, disease activity, and damage assessment, suggesting the use of a validated disease activity score per visit and annual damage score. Strong recommendations were made for cardiovascular risk assessment and measuring anti-Ro and anti-La antibodies in the peripartum period and conditional recommendations for osteoporosis and osteonecrosis. Two conditional recommendations were made for peripartum assessments, 1 for cervical cancer screening and 2 for hepatitis B and C screening. A strong recommendation was made for annual influenza vaccination.Conclusion.These are considered the first guidelines using the GRADE method for the monitoring of SLE. Existing evidence is largely of low to moderate quality, resulting in more conditional than strong recommendations. Additional rigorous studies and special attention to pediatric SLE populations and patient preferences are needed.

Objective.Systemic sclerosis (SSc) may overlap with systemic lupus erythematous (SLE). Little is known about the epidemiology, clinical characteristics, and survival of SSc-SLE overlap. We evaluated the prevalence of SSc-SLE overlap and differences in SSc characteristics, and compared survival with SSc without SLE.Methods.A cohort study was conducted including subjects who fulfilled the American College of Rheumatology (ACR)/European League Against Rheumatism classification criteria for SSc and/or the ACR criteria for SLE. The primary outcome was time from diagnosis to all-cause mortality. Survival was evaluated using Kaplan-Meier and Cox proportional hazard models.Results.We identified 1252 subjects (SSc: n = 1166, SSc-SLE: n = 86) with an SSc-SLE prevalence of 6.8%. Those with SSc-SLE were younger at diagnosis (37.9 yrs vs 47.9 yrs, p < 0.001), more frequently East Asian (5.5% vs 20%) or South Asian (5.1% vs 12%), had lupus anticoagulant (6% vs 0.3%, p < 0.001), anticardiolipin antibody (6% vs 0.9%, p < 0.001), and pulmonary arterial hypertension (PAH; 52% vs 31%, p < 0.001). Those with SSc-SLE less frequently had calcinosis (13% vs 27%, p = 0.007), telangiectasia (49% vs 75%, p < 0.001), and diffuse subtype (12% vs 35%, p < 0.001). There were no significant differences in the occurrence of renal crisis (7% vs 7%), interstitial lung disease (ILD; 41% vs 34%), and digital ulcers (38% vs 32%). Those with SSc-SLE had better median survival time (26.1 vs 22.4 yrs), but this was not statistically significant (log-rank p = 0.06). Female sex and diffuse subtype attenuated survival differences between groups (HR 1.07, 95% CI 0.67–1.67).Conclusion.Patients with SSc-SLE are younger at diagnosis, more frequently have PAH, and less frequently have cutaneous manifestations of SSc. They should be monitored for ILD, renal crisis, and digital ulcers.