Residual disease activity and treatment intensification in systemic lupus erythematosus: A cross-sectional study to quantify the need for new therapies.

OBJECTIVE: The proportion of SLE patients with residual disease activity in routine settings is variable. We assessed disease activity state in patients during their most recent visit, and whether patients with residual activity were offered therapy intensification. METHODS: Cross-sectional study of consecutive lupus patients in three tertiary centers. Patients were categorized as: i) remission off-therapy, ii) remission on-therapy, iii) low disease activity, and iv) non-optimally controlled disease. Multivariable regression identified factors associated with treatment intensification and ROC analysis calculated the accuracy of SLEDAI-2K to predict this intensification. RESULTS: Three hundred and thirty-two patients were included [93.1% female, mean (SD) age 48.5 (14.7) years, median (IQR) disease duration 6.5 (12.4) years]. Mean (SD) total and clinical SLEDAI at last visit were 3.7 (3.0) and 3.0 (2.9), respectively. Although 23.2% of patients were in remission, 40.1% were categorized as non-optimally controlled disease (79.2% due to SLEDAI-2K > 4), but less than 50% of them were offered therapy intensification. Proteinuria (OR 6.78, 95% CI 2.06-22.25), arthritis (OR 5.48, 95% CI 3.20-9.40), and rash (OR 3.23, 95% CI 1.81-5.75) were associated with intensification of therapy, but the accuracy of either total or clinical SLEDAI to predict it was moderate (ROC area under the curve 0.761 and 0.779, respectively). CONCLUSIONS: About 40% of patients have evidence of residual disease activity and could qualify for novel treatments. Most treatment changes were triggered by active renal, joint, and skin disease, whereas the predictive value of SLEDAI-2K as a metric of disease activity was modest.

Tailored treatment strategies and future directions in systemic lupus erythematosus.

Systemic lupus erythematosus (SLE) represents a diagnostic and therapeutic challenge for physicians due to its protean manifestations and unpredictable course. The disease may manifest as multisystemic or organ-dominant and severity at presentation may vary according to age at onset (childhood-, adult- or late-onset SLE). Different manifestations may respond variably to different immunosuppressive medications and, even within the same organ-system, the severity of inflammation may vary from mild to organ-threatening. Current "state-of-the-art" in SLE treatment aims at remission or low disease activity in all organ systems. Apart from hydroxychloroquine and glucocorticoids (which should be used with caution), the choice of the appropriate immunosuppressive agent should be individualized and depend on the prevailing manifestation, severity stratification and patient childbearing potential. In this review, we provide an overview of therapeutic options for the various organ manifestations and severity patterns of the disease, different phenotypes (such as multisystem versus organ-dominant disease), as well as specific considerations, including lupus with antiphospholipid antibodies, childhood and late-onset disease, as well as treatment options during pregnancy and lactation.

Quality indicators for systemic lupus erythematosus based on the 2019 EULAR recommendations: development and initial validation in a cohort of 220 patients.

BACKGROUND: Quality of care is receiving increased attention in systemic lupus erythematosus (SLE). We developed quality indicators (QIs) for SLE based on the 2019 update of European League Against Rheumatism recommendations. METHODS: A total of 44 candidate QIs corresponding to diagnosis, monitoring and treatment, were independently rated for validity and feasibility by 12 experts and analysed by a modified Research and Development Corporation/University of California Los Angeles model. Adherence to the final set of QIs and correlation with disease outcomes (flares, hospitalisations and organ damage) was tested in a cohort of 220 SLE patients with a median monitoring of 2 years (IQR 2-4). RESULTS: The panel selected a total of 18 QIs as valid and feasible. On average, SLE patients received 54% (95% CI 52.3% to 56.2%) of recommended care, with adherence ranging from 44.7% (95% CI 40.8% to 48.6%) for diagnosis-related QIs to 84.3% (95% CI 80.6% to 87.5%) for treatment-related QIs. Sustained remission or low disease activity were achieved in 26.8% (95% CI 21.1% to 33.2%). Tapering of prednisone dose to less than 7.5 mg/day was achieved in 93.6% (95% CI 88.2% to 97.0%) while 73.5% (95% CI 66.6% to 79.6%) received the recommended hydroxychloroquine dose. Higher adherence to monitoring-related QIs was associated with reduced risk for a composite adverse outcome (flare, hospitalisation or damage accrual) during the last year of observation (OR 0.97 per 1% adherence rate, 95% CI 0.96 to 0.99). CONCLUSION: We developed QIs for assessing and improving the care of SLE patients. Initial real-life data suggest face validity, but a variable degree of adherence and a need for further improvement.

Demyelinating Syndromes in Systemic Lupus Erythematosus: Data From the "Attikon" Lupus Cohort.

Background: The demyelinating syndromes of the central nervous system (CNS) that occur in the context of systemic lupus erythematosus (SLE) may represent a manifestation of neuropsychiatric lupus (NPSLE) or an overlap of SLE and multiple sclerosis (MS). The differential diagnosis between the two entities has important clinical implications because the therapeutic management differs. Objectives: To characterize CNS demyelinating syndromes in a large SLE cohort as neuropsychiatric SLE (NPSLE) or SLE-MS overlap using a multidisciplinary approach and existing diagnostic (for MS) and classification criteria (for SLE). Methods: Patients from the "Attikon" lupus cohort (n = 707) were evaluated for demyelinating syndromes. Clinical, laboratory, and neuroimaging data were recorded for each patient. Following multidisciplinary evaluation and application of criteria, the demyelinating syndrome was attributed to either SLE or MS. Patients with transverse myelitis were not included in this study. Results: We identified 26 patients with demyelinating syndromes (3.7%). Of them, 12 were diagnosed as primary SLE-demyelination (46.2%) and 14 as overlap SLE-MS (53.8%). The two groups did not differ with respect to rheumatologic and neurologic manifestations or autoantibodies. SLE patients with demyelination manifested mild extra-CNS disease mainly involving joints and skin, while severe non-CNS manifestations were rare. However, these patients were less likely to have elevated IgG index (OR 0.055 95% CI: 0.008-0.40) and positive oligoclonal bands (OR 0.09 95% CI: 0.014-0.56), as well as brain lesions in the spinal cord, infratentorial, periventricular, and juxtacortical regions. A single brain region was affected in 9 patients with SLE-demyelination (75%), while all patients with MS-SLE had multiple affected brain regions. MS-SLE overlap was associated with an increased likelihood of neurologic relapses (OR 18.2, 95% CI: 1.76-188), while SLE-demyelination patients were less likely to exhibit neurological deficits (EDSS >0) at the last follow-up visit (50 vs. 78.6% in SLE-MS, respectively). Conclusions: Demyelination in the context of SLE follows a more benign course compared to a frank SLE-MS overlap. Extension of follow-up will ascertain whether patients with SLE-demyelination evolve to MS, or this is a bona fide NPSLE syndrome.

Acute Abdominal Situations as Presenting or Flaring Manifestations of Systemic Lupus Erythematosus: A Case Series.

Systemic lupus erythematosus (SLE)is a multisystem autoimmune disease, characterized by clinical heterogeneity, ranging from mild to severe, life-threatening manifestations. Although gastrointestinal (GI) symptoms are frequently encountered during disease course (mainly associated with complications of medication or infection), primary GI involvement due to SLE is rare. Among variable presentations, lupus abdominal serositis (defined as peritonitis if accompanied by symptoms and signs of acute abdomen) and lupus enteritis/mesenteric vasculitis are causes of SLE-related acute abdominal pain. They occur, although not always, in the context of high disease activity and prompt diagnosis and treatment is necessary due to their potential severe complications. However, the diagnosis of these manifestations remains challenging even for experts, especially in cases of "organ-dominant" lupus flares. Exclusion of these rare manifestations from classification criteria increases the likelihood of misdiagnosis and highlights the inherent limitations of classification criteria when the latter are used for diagnosis. Urgent abdominal computed tomography can lead to a prompt diagnosis of these lupus manifestations, especially characteristic for lupus mesenteric vasculitis. Herein, we describe four cases of patients with lupus flare, presenting with acute abdominal manifestations and highlight the potential complexity of diagnostic approach in such situations.

Periaortitis and diffuse subendocardial vasculitis in a patient with systemic lupus erythematosus - Lupus flare or a coexisting disease?

Systemic lupus erythematosus (SLE) is a heterogeneous disease with a broad spectrum of clinical manifestations. Periaortitis is a rare disorder which may manifest isolated or in association with other autoimmune diseases, including SLE. Another rare, yet severe cardiovascular manifestation of lupus is diffuse subendocardial vasculitis (DSV), which should be suspected in patients presenting with myocardial hypokinesis, impaired ejection fraction and normal coronary angiography. Cardiovascular Magnetic Resonance (CMR) imaging is crucial to distinguish between DSV and lupus myocarditis, which should also be included in the differential diagnosis. Herein, we describe a case of a female patient with pre-existing SLE, who presented with both periaortitis and DSV, and discuss the diagnostic challenges associated with these rare manifestations.