Mania in an individual with Systemic Lupus Erythematosus – A case report

Neuropsychiatric manifestations are common and occur in around 14-80% of patients with SLE. No particular neurologic or psychiatric manifestation is characteristic of SLE and the form and pattern of neuropsychiatric symptoms vary significantly. The American College of Rheumatology (ACR) Nomenclature provides case definition for 19 neuropsychiatric syndromes seen in SLE. However, these case definitions were not found to be effective in differentiating neuropsychiatric SLE (NPSLE) patients from those with neuropsychiatric manifestations not associated with SLE.Here we present a case of mania in a patient with SLE and discuss the differential diagnosis of neuropsychiatric manifestations of SLE and primary mood disorder. Symptoms of neuropsychiatric SLE vary significantly and psychiatric disturbances in a patient with SLE is a diagnosis of exclusion where other possibilities have to be considered including an independent comorbid psychiatric disorder. This case highlights the difficulty in the diagnostic process and the need for more studies on the differences between primary psychiatric disorders and neuropsychiatric SLE.

Stercoral Colitis in a Patient With Pediatric-Onset Systemic Lupus Erythematosus: Case Analysis and Review of the Literature

Systemic lupus erythematosus (SLE) is an autoantibody-related disease that affects multiple organs. Stercoral colitis (SC) is a rare type of inflammatory colitis with a high mortality rate. Here, we report the first case of pediatric-onset lupus in a case complicated by stercoral colitis. We also conducted a literature review of patients with SC under 30 years old to provide useful clues for rapid diagnosis at a young age. A 28-year-old female with a history of lupus and neuropsychiatric SLE was admitted with severe abdominal pain. She was found to have stercoral colitis during surgery. Two years later, the patient underwent Hartman's operation due to ischemia of the colon. In addition, 10 patients younger than 30 years old with a diagnosis of SC were analyzed based on clinical presentation, physical examination, laboratory exam, imaging and treatment. All cases had a favorable outcome without mortality. Stercoral colitis is a rare but lethal complication, emphasizing the importance of a multidisciplinary approach. Differential diagnosis should include stercoral colitis for patients with SLE developing unexplained sharp abdominal pain.

Complete resolution of juvenile neuropsychiatric lupus with low dose rituximab

Nervous system involvement leads to high mortality in juvenile systemic lupus erythematosus. We present the case of a 12-year-old girl who was admitted with a history of recurrence of fever, cervical swellings, seizure, and delirium. Approximately 6 months back, she was started on antitubercular therapy (ATT) for fever and granulomatous lymphadenitis. She developed a recurrence of fever, new cervical swellings, seizures, and delirium while she was continuing ATT. Magnetic Resonance Imaging brain revealed multiple hyperintensities in bilateral basal ganglia, temporal, and hippocampal regions. The patient was diagnosed to have lupus based on clinical features, positive antinuclear antibody, positive double-stranded DNA antibody, and hypocomplementemia. To avoid cyclophosphamide-related gonadotoxicity in this young girl, Rituximab was given. She was treated with two doses of Rituximab and there was complete resolution of her neuropsychiatric SLE. Rituximab can be considered over cyclophosphamide in children to avoid gonadotoxicity.

Association of lipoproteins and thyroid hormones with cognitive dysfunction in patients with systemic lupus erythematosus

Background Neuropsychiatric manifestations occur in up to 75% of adult systemic lupus erythematosus (SLE) patients and are one of the major causes of death in SLE patients. Cognitive dysfunction is a typical clinical feature of neuropsychiatric SLE (NPSLE), which seriously affects the quality of life of patients. Dyslipidaemia and thyroid symptoms, which are prevalent in SLE patients, have both been related to neuropsychiatric disturbances, including significant psychiatric and cognitive disturbances. This study aimed to investigate whether cognitive dysfunction in patients with SLE was related to the expression of serum thyroid hormone and lipoprotein levels. Methods A total of 121 patients with SLE and 65 healthy controls (HCs) at Nanjing Drum Tower Hospital completed a cognitive function test, and 81 SLE patients were divided into a high-cognition (n = 33) group and a low-cognition group (n = 48). The clinical and laboratory characteristics of the patients were compared; moreover, correlations between serum HDL-C, LDL-C, F-T3 and F-T4 levels and cognitive function were analysed. Serum levels of APOE, APOA1, IGF-1, and IGFBP7 in 81 patients were detected by ELISA, and the correlation between these four proteins and cognition was analysed separately. Results The patients with SLE with abnormal cognitive function were less educated than the HCs. For low-cognition patients, the levels of albumin, F-T3 (P < 0.05) and F-T4 decreased, while D-dimer, anti-dsDNA antibody, and IgM levels increased. Serum F-T3 and F-T4 levels positively correlated with cognition. Furthermore, serum protein levels of APOE and APOA1 showed no difference between the high- and low-cognition groups. However, the serum APOE levels were negatively correlated with line orientation scores, and APOA1 levels were positively correlated with coding scores. Conclusions Serum F-T3 and F-T4 levels were both positively correlated with four indexes of cognition (language was the exception), while serum APOE levels were negatively correlated with line orientation scores, APOA1 levels were positively correlated with coding scores, and IGFBP7 levels were negatively correlated with figure copy scores. These results demonstrated that F-T3 and F-T4 might be clinical biomarkers of cognitive dysfunction in SLE.

AB0287 EFFECTS OF HYDROXYCHLOROQUINE ON PERIPHERAL BLOOD CYTOKINE EXPRESSION ASSOCIATED WITH ATHEROSCLEROSIS IN SYSTEMIC LUPUS ERYTHEMATOSUS

Background:In systemic lupus erythematosus(SLE), a higher frequency of atherosclerotic lesions is associated with a poor life prognosis (1). Hydroxychloroquine (HCQ) has been reported to improve the prognosis of life and dyslipidemia in SLE (2), and the mechanism has been unclear.Objectives:To determine the effect of HCQ treatment on serum cytokines associated with atherosclerosis in SLE.Methods:SLE patients who received additional HCQ and maintained low disease activity between January 2016 and September 2020 were included in this study. Disease activity was assessed by SLEDAI, CLASI and LLDAS, and serum complement titers, anti-ds-DNA antibodies, serum insulin and serum cytokines (adiponectin, resistin and leptin) were analyzed before and after HCQ treatment.Results:Fifty-four patients (3 males, 51 females, mean age 41.9±12.8 years) were included (Table 1). Thirty-two patients achieved LLDAS at baseline. Serum adiponectin and insulin levels were significantly increased after 3 months of HCQ treatment compared to baseline, and serum resistin levels were significantly lower (Figure 1). Patients with a history of renal disease had greater degree of changes in serum adiponectin and resistin levels. Among SLE patients who did not achieve LLDAS at baseline, those who still did not achieve LLDAS after 3 months had significantly lower serum leptin levels before HCQ treatment than those who achieved it after 3 months.The change of serum resistin levels correlated with those of serum S100A8 levels (r=0.5, p=0.0001).Conclusion:Additional HCQ treatment in SLE patients improves lipid abnormalities. HCQ may improve prognosis by controlling disease activity in SLE and reducing risk factors for atherosclerosis.References:[1]Gregory Katz, et al. Systemic Lupus Erythematosus and Increased Prevalence of Atherosclerotic Cardiovascular Disease in Hospitalized Patients. Mayo Clin Proc. 2019; 94:1436-1443.[2]Laura Durcan, et al. Longitudinal Evaluation of Lipoprotein Parameters in Systemic Lupus Erythematosus Reveals Adverse Changes with Disease Activity and Prednisone and More Favorable Profiles with Hydroxychloroquine Therapy. J Rheumatol. 2016; 43: 745–750.Table 1.Characteristics of SLE patients enrolled in this studyCharacteristicsn=54, no.(%)Female, no(%)51(94)Age, years, mean±SD41.9±12.8Disease duration, years, mean±SD15.1±11.1Past involvementRenal involvement23 (43)NPSLE5 (9)ComplicationAPS10 (19)Dyslipidemia2 (4)Diabetes 1 (2)Concomitant immunosuppressive treatmentsPrednisone No.(%)46 (85) Median Dosage, mg/day (range)5.0 (1-10)Disease activitySLENA-SLEDAI score3.9±2.0 Current skin involvement30 (56) anti-dsDNA positive, no(%)21 (39)low complement, no(%)29 (54)Anti-dsDNA positive means anti ds-DNA titer increases over 12 IU/mlLow complement means any of C3, C4 and CH50 decreases to less 68mg/dl, less 12mg/dl, 30U/ml.APS: Anti-phospholipid antibody syndrome, NPSLE: neuropsychiatric SLE,Disclosure of Interests:None declared

MRI-based classification of neuropsychiatric systemic lupus erythematosus patients with self-supervised contrastive learning

Introduction/PurposeSystemic lupus erythematosus (SLE) is a chronic auto-immune disease with a broad spectrum of clinical presentations, including heterogeneous and uncommon neuropsychiatric (NP) syndromes. Accurate diagnosis of neuropsychiatric SLE (NPSLE) is challenging due to lack of clinically useful biomarkers. Despite structural brain abnormalities on MRI in NPSLE being a common finding, a robust link between structural abnormalities and NPSLE has not been established, thus their contribution to the distinction between NPSLE patients and patients in which the NP symptoms are not primarily attributed to SLE is limited. Self-supervised contrastive learning algorithms do not require labels, and have been shown to be useful in classification tasks in rare diseases with limited number of datasets. The aim of our study was to apply self-supervised contrastive learning on T1-weighted images acquired from a well-defined cohort of SLE patients to distinguish between SLE patients with NP symptoms due to the disease (NPSLE) or and SLE patients with similar symptoms due to other causes (non-NPSLE).Subjects and Methods163 patients were included. We used 3T MRI T1-weighted images registered to the MNI152 template. The training set comprised 68 non-NPSLE and 34 NPSLE patients. During the training procedure, we applied random geometric transformations (cropping, left-right flipping and rotations) between iterations to enrich our data sets. Our ML pipeline consisted of convolutional base encoder and linear projector. To test the classification task, the projector was removed and one linear layer was measured. We trained the encoder and projector with the Normalized Temperature-scaled Cross Entropy Loss (NT-xent) loss function. We performed a Monte Carlo validation that consisted of 6 repeated random sub-samplings each using a random selection of a small group of samples from each group.ResultsIn the 6 trials described above, between 79% and 83% of the patients were correctly classified as NPSLE or non-NPSLE. For a qualitative evaluation of spatial distribution of the common features found in the NPSLE population, Gradient-weighted Class Activation Maps (Grad-CAM) were examined voxel-wise. Thresholded Grad-CAM maps show areas of common features identified for the NPSLE cohort, with no such communality found for the non-NPSLE group.Discussion/conclusionThe self-supervised contrastive learning model was effective in capturing diagnostic brain MRI features from a limited but well-defined cohort of SLE patients with NP symptoms. The interpretation of the Grad-CAM results is not straightforward, but points to involvement of the lateral and third ventricles, periventricular white matter and basal cisterns. We believe that the common features found in the NPSLE population in this study indicate a combination of tissue loss, local atrophy and to some extent that of periventricular white matter lesions, which are commonly found in NPSLE patients and appear hypointense on T1-weighted images.

Anxiety and depression severity in neuropsychiatric SLE are associated with perfusion and functional connectivity changes of the frontolimbic neural circuit: a resting-state f(unctional) MRI study

ObjectiveTo examine the hypothesis that perfusion and functional connectivity disturbances in brain areas implicated in emotional processing are linked to emotion-related symptoms in neuropsychiatric SLE (NPSLE).MethodsResting-state fMRI (rs-fMRI) was performed and anxiety and/or depression symptoms were assessed in 32 patients with NPSLE and 18 healthy controls (HC). Whole-brain time-shift analysis (TSA) maps, voxel-wise global connectivity (assessed through intrinsic connectivity contrast (ICC)) and within-network connectivity were estimated and submitted to one-sample t-tests. Subgroup differences (high vs low anxiety and high vs low depression symptoms) were assessed using independent-samples t-tests. In the total group, associations between anxiety (controlling for depression) or depression symptoms (controlling for anxiety) and regional TSA or ICC metrics were also assessed.ResultsElevated anxiety symptoms in patients with NPSLE were distinctly associated with relatively faster haemodynamic response (haemodynamic lead) in the right amygdala, relatively lower intrinsic connectivity of orbital dlPFC, and relatively lower bidirectional connectivity between dlPFC and vmPFC combined with relatively higher bidirectional connectivity between ACC and amygdala. Elevated depression symptoms in patients with NPSLE were distinctly associated with haemodynamic lead in vmPFC regions in both hemispheres (lateral and medial orbitofrontal cortex) combined with relatively lower intrinsic connectivity in the right medial orbitofrontal cortex. These measures failed to account for self-rated, milder depression symptoms in the HC group.ConclusionBy using rs-fMRI, altered perfusion dynamics and functional connectivity was found in limbic and prefrontal brain regions in patients with NPSLE with severe anxiety and depression symptoms. Although these changes could not be directly attributed to NPSLE pathology, results offer new insights on the pathophysiological substrate of psychoemotional symptomatology in patients with lupus, which may assist its clinical diagnosis and treatment.

Fatigue in patients with systemic lupus erythematosus and neuropsychiatric symptoms is associated with anxiety and depression rather than inflammatory disease activity

Introduction We aimed to investigate risk factors for fatigue in patients with systemic lupus erythematosus (SLE) and neuropsychiatric symptoms in order to identify potential interventional strategies. Methods Patients visiting the neuropsychiatric SLE (NPSLE) clinic of the Leiden University Medical Center between 2007–2019 were included. In a multidisciplinary consensus meeting, SLE patients were classified as having neuropsychiatric symptoms of inflammatory origin (inflammatory phenotype) or other origin (non-inflammatory phenotype). Fatigue was assessed with the SF-36 vitality domain (VT) since 2007 and the multidimensional fatigue inventory (MFI) and visual analogue scale (VAS) since 2011. Patients with a score on the SF-36 VT ≥1 standard deviation (SD) away from the mean of age-related controls of the general population were classified as fatigued; patients ≥2 SD away were classified as extremely fatigued. Disease activity was measured using the SLE disease activity index-2000. The influence of the presence of an inflammatory phenotype, disease activity and symptoms of depression and anxiety as measured by the hospital anxiety and depression scale (HADS) was analyzed using multiple regression analyses corrected for age, sex and education. Results 348 out of 371 eligible patients filled in questionnaires and were included in this study . The majority was female (87%) and the mean age was 43 ± 14 years. 72 patients (21%) had neuropsychiatric symptoms of an inflammatory origin. Fatigue was present in 78% of all patients and extreme fatigue was present in 50% of patients with an inflammatory phenotype vs 46% in the non-inflammatory phenotype. Fatigue was similar in patients with an inflammatory phenotype compared to patients with a non-inflammatory phenotype on the SF-36 VT (β: 0.8 (95% CI −4.8; 6.1) and there was less fatigue in patients with an inflammatory phenotype on the MFI and VAS (β: −3.7 (95% CI: −6.9; −0.5) and β: −1.0 (95% CI −1.6; −0.3)). There was no association between disease activity and fatigue, but symptoms of anxiety and depression (HADS) associated strongly with all fatigue measurements. Conclusion This study suggests that intervention strategies to target fatigue in (NP)SLE patients may need to focus on symptoms of anxiety and depression rather than immunosuppressive treatment.

A novel therapeutic approach using the Zipper method to treat chorea in a pediatric-onset systemic lupus erythematosus patient

Pediatric-onset systemic lupus erythematosus is among the prototypic systemic autoimmune diseases seen in children. Although the neuropsychiatric involvement rate varies during the course of the disease, it is an important cause of morbidity and mortality. The clinical picture of neuropsychiatric SLE (NPSLE) is highly variable, and neurological features can precede systemic findings, leading to some diagnostic difficulties. NPSLE requires early and aggressive immunosuppressive therapy. Some patients can be resistant to immunosuppressive therapy. Chorea is a rare manifestation that occurs in 1.2%–2% of SLE patients and can result from an immunologically mediated mechanism, antiphospholipid autoantibodies or ischemia. Herein we present the first case of pediatric-onset SLE diagnosed with central nervous system involvement and treated with Zipper method. The Zipper method is a new immunomodulation treatment. The clinical findings of the patient, which were resistant to corticosteroids and cyclophosphamide, resolved by this novel treatment.