Type I Interferons in Autoimmunity: Implications in Clinical Phenotypes and Treatment Response.

Type I interferon (IFN-I) is thought to play a role in many systemic autoimmune diseases. IFN-I pathway activation is associated with pathogenic features, including the presence of autoantibodies and clinical phenotypes such as more severe disease with increased disease activity and damage. We will review the role and potential drivers of IFN-I dysregulation in 5 prototypic autoimmune diseases: systemic lupus erythematosus, dermatomyositis, rheumatoid arthritis, primary Sjögren syndrome, and systemic sclerosis. We will also discuss current therapeutic strategies that directly or indirectly target the IFN-I system.

Cross-Cultural Adaptation and Validation of the Methotrexate Intolerance Severity Score Questionnaire in Portuguese (Brazil) for Children and Adolescents with Juvenile Idiopathic Arthritis.

The Methotrexate (MTX) Intolerance Severity Score (MISS) questionnaire has been developed to identify MTX adverse events in juvenile idiopathic arthritis (JIA). The objective of this study was to translate and validate MISS into Brazilian Portuguese for children and adolescents. The MISS was translated into Portuguese following the standardized guidelines. We analyzed the following psychometric properties: acceptability, internal consistency, test-retest reproducibility, relative-child reliability, and external criterion and discriminant validity. We included 138 JIA patients (age: 8-18 years) and 108 relatives who took less than 5 min to answer MISS. Reproducibility tested after 15 days was good, with a kappa > 0.76. We observed good internal consistency (Cronbach's coefficient 0.75-0.87 (patients) and 0.75-0.79 (relatives)). Reliability between patients and relatives was good except for stomachache and restlessness. Cut-off points of 5 and 6 had good sensitivity (84 and 71, respectively) and specificity (80 and 87, respectively). Using a cut-off value of 6, we observed 86 (62.3%) MTX-intolerant patients. In conclusion, MISS is a viable and practical tool for routine clinical care to identify MTX intolerance in JIA. Parents do not easily identify stomachache and restlessness as adverse MTX events.

Microstructural Changes in the Corpus Callosum in Systemic Lupus Erythematous.

Central nervous system (CNS) involvement in childhood-onset systemic lupus erythematosus (cSLE) occurs in more than 50% of patients. Structural magnetic resonance imaging (MRI) has identified global cerebral atrophy, as well as the involvement of the corpus callosum and hippocampus, which is associated with cognitive impairment. In this cross-sectional study we included 71 cSLE (mean age 24.7 years (SD 4.6) patients and a disease duration of 11.8 years (SD 4.8) and two control groups: (1) 49 adult-onset SLE (aSLE) patients (mean age of 33.2 (SD 3.7) with a similar disease duration and (2) 58 healthy control patients (mean age of 29.9 years (DP 4.1)) of a similar age. All of the individuals were evaluated on the day of the MRI scan (Phillips 3T scanner). We reviewed medical charts to obtain the clinical and immunological features and treatment history of the SLE patients. Segmentation of the corpus callosum was performed through an automated segmentation method. Patients with cSLE had a similar mid-sagittal area of the corpus callosum in comparison to the aSLE patients. When compared to the control groups, cSLE and aSLE had a significant reduction in the mid-sagittal area in the posterior region of the corpus callosum. We observed significantly lower FA values and significantly higher MD, RD, and AD values in the total area of the corpus callosum and in the parcels B, C, D, and E in cSLE patients when compared to the aSLE patients. Low complement, the presence of anticardiolipin antibodies, and cognitive impairment were associated with microstructural changes. In conclusion, we observed greater microstructural changes in the corpus callosum in adults with cSLE when compared to those with aSLE. Longitudinal studies are necessary to follow these changes, however they may explain the worse cognitive function and disability observed in adults with cSLE when compared to aSLE.

Cognitive Performance in Patients with Systemic Lupus Erythematosus Using the Ped-ANAM.

Computerized batteries have been widely used to investigate cognitive impairment (CI) in patients with SLE. The aim of this study was to evaluate the cognitive performance of patients with SLE in relation to healthy controls using the Pediatric Automated Neuropsychological Assessment Metrics (Ped-ANAM) battery. In addition, we aimed to examine differences in Ped-ANAM scores according to age of disease onset, presence of disease activity, and disease damage. We included 201 consecutive adult-onset (aSLE) and childhood-onset SLE (cSLE) patients who were being followed at the hospital's rheumatology outpatient clinic and 177 healthy controls. We applied the percentage of correct answers on the Ped-ANAM subtests and the Performance Validity Index (PVI) metric and correlated them with the Systemic Lupus Erythematosus Disease Activity Index (SLEDAI) and Systemic Lupus Erythematosus Damage Index (SDI). Then, we established their relationships with neuropsychiatric systemic lupus erythematosus (NPSLE). We observed CI in a total of 38 (18.9%) SLE patients and 8 (4.5%) healthy controls (p < 0.001). CI was observed in eight (19.5%) cSLE patients and 32 (20%) aSLE patients (p = 0.8175). Individual analysis of the aSLE subtests showed a significant difference in all subtests compared to healthy controls; the greatest differences were in matching to sample (p < 0.001) and memory search ( p < 0.001). In the cSLE group, we observed a difference in the code substitution subtests (p = 0.0065) compared to the healthy controls. In the evaluation of clinical outcomes, disease activity was significantly correlated with CI in cSLE (r = 0.33; p = 0.042) and aSLE (r = 0.40; p = 0.001). We also observed an association between disease activity and neuropsychiatric manifestations (p = 0.0012) in aSLE. In conclusion, we determined that cognitive dysfunction, mainly in memory and attention, was more prevalent in patients with SLE. In both the cSLE and aSLE groups, disease activity was associated with worse cognitive function. This is the first study to use the Ped-ANAM in Brazil. Longitudinal studies are necessary to determine how the Ped-ANAM will perform over time.

Neuropsychiatric manifestations in childhood-onset systemic lupus erythematosus.

Neuropsychiatric manifestations occur frequently and are challenging to diagnose in childhood-onset systemic lupus erythematosus (SLE). Most patients with childhood-onset SLE have neuropsychiatric events in the first 2 years of disease. 30-70% of patients present with more than one neuropsychiatric event during their disease course, with an average of 2-3 events per person. These symptoms are associated with disability and mortality. Serum, cerebrospinal fluid, and neuroimaging findings have been described in childhood-onset SLE; however, only a few have been validated as biomarkers for diagnosis, monitoring response to treatment, or prognosis. The aim of this Review is to describe the genetic risk, clinical and neuroimaging characteristics, and current treatment strategies of neuropsychiatric manifestations in childhood-onset SLE.

Predicting lupus flares: epidemiological and disease related risk factors.

Introduction: Systemic lupus erythematosus (SLE) is a chronic autoimmune disorder, characterized by a relapsing and remitting pattern of disease activity in majority of the patients. Areas covered: This narrative review provides an overview of flare definition, major flare mimics, and the burden of flares in SLE. The authors highlight epidemiology and disease-related risk factor for flares and discuss strategies to reduce flares in SLE. Articles were selected from Pubmed searches conducted between June 2020 and September 2020. Expert opinion: Prolonged clinical remission is observed in approximately 20% of SLE patients flare over the course of the disease. Studies have shown that low disease activity is a good target in SLE, with similar risk of flares, mortality, and quality of life when compared to patients in remission. Clinical and immunological features have shown inconsistent results to identify patients at risk of flares in different cohorts. Cytokine, in serum and urine, has shown promising results to predict flares. However to be useful in clinical practice, they have to be simple, easy, and cost-effective. Future efforts in this direction will allow a more personalized treatment plan for SLE patients, reducing the burden associated with flares.

Chronic inflammatory demyelinating polyradiculoneuropathy associated with systemic lupus erythematosus.

BACKGROUND: Chronic Inflammatory Demyelinating Polyradiculoneuropathy (CIDP) is an uncommon subtype of peripheral neuropathy (PN) and especially when associated with systemic lupus erythematosus (SLE). There are few reports characterizing PN-associated to SLE, in particular CIDP. This study reviewed the frequency and profile of SLE-related CIDP in our cohort and in the literature and propose a treatment scheme for CIDP associated with SLE. METHOD: We reviewed our database to identify patients with CIDP and SLE. The literature was also reviewed following the guidelines of PRISMA and using the terms "Polyradiculoneuropathy", "Chronic inflammatory demyelinating polyradiculoneuropathy", "CIDP", "Systemic lupus erythematosus", "SLE", "Autoimmune diseases of the nervous system" until December 2019. Selected articles were published in English. RESULTS: We identified 3 patients with SLE and CIDP in our cohort of 1,349 patients with SLE (0.2%). All patients were female, aged between 30 and 44 years and 2 (66.7%) had active disease in other organs. In the literature, we identified additional 16 patients. A predominance of women with disease activity, specially nephritis and hematological involvement, was observed. Treatment schemes are diverse, including corticosteroids and immunosuppressive drugs. CONCLUSION: Although rare, CIDP has increased frequency in SLE. Women and younger age should rise suspicion of an underlying autoimmune disease. We suggest that CIDP should be included as a possible neuropsychiatric manifestation in SLE.

Trisomy X in a patient with childhood-onset systemic lupus erythematosus.

Childhood-onset systemic lupus erythematosus (cSLE) is a rare, chronic and systemic autoimmune disease generally with a more severe clinical phenotype than the adult-onset SLE. In both conditions, it is known that females are predominantly affected; therefore, the possible overlap of SLE and sex chromosomal abnormalities has attracted attention. Our case report describe the clinical manifestations and immunological profile of a Brazilian female with cSLE and trisomy X. The 22 year-old patient, diagnosed with cSLE at age of 11, present some features related to 47, XXX, such as difficulties at school and communication, although this was not enough to investigate for chromosome abnormalities. Cytoscan HD array screening allowed the comprehensive diagnosis for this patient. We also characterized her ancestral composition, showing that she has 6.2% higher African component than the mean from health subjects from the same geographical area. This report reinforces the role of the X chromosome dose effect for sex bias in SLE, as well as the importance of African ancestry composition in cLES. It also throws lights upon the application of high-throughput molecular analysis in a large scale cohort can be useful to detect the impact of the genomic findings for more accurate epidemiological data.

Definition of NPSLE: Does the ACR Nomenclature Still Hold?

Systemic lupus erythematosus (SLE) patients have frequently neuropsychiatric manifestations. From the first description of coma in 1875, a variety of manifestations has been described to occur in SLE. However, the lack of standardization reduced the comparability of published studies. In 1999, the American College of Rheumatology published guidelines to define neuropsychiatric nomenclature in SLE. This was the first step toward uniform diagnostic criteria. Several studies have been published since then applying the ACR criteria and frequencies of different manifestations can now be compared between cohorts. Although these criteria are diagnostic, therapeutic approach to different manifestations varies according to nature and severity of the manifestations. Herby, we will review the different definition for NPSLE published, and determine advantages and limitation.