The Outcomes of an e-Wellness Program for Lupus Patients in Thailand: A Participatory Action Research Approach.

OBJECTIVES: Systemic lupus erythematosus (SLE) or lupus patients usually experience various physical and psychological challenges. Since the coronavirus disease 2019 pandemic, these challenges have become even harsher. Using the participatory action research approach, this study evaluated how an e-wellness program (eWP) impacted SLE-related knowledge and health behaviors, mental health, and quality of life among lupus patients in Thailand. METHODS: A 1-group, pretest-posttest design study was conducted among a purposive sample of lupus patients who were members of Thai SLE Foundation. The 2 main intervention components were: (1) online social support, and (2) lifestyle and stress management workshops. Sixty-eight participants completed all the study requirements, including the Physical and Psychosocial Health Assessment questionnaire. RESULTS: After being in the eWP for 3 months, participants' mean score for SLE-related knowledge increased significantly (t=5.3, p<0.001). The increase in sleep hours was statistically significant (Z=-3.1, p<0.01), with the percentage of participants who slept less than 7 hours decreasing from 52.9% to 29.0%. The percentage of participants reporting sun exposure decreased from 17.7% to 8.8%. The participants also reported significantly lower stress (t(66)=-4.4, p<0.001) and anxiety (t(67)=-2.9, p=0.005). The post-eWP quality of life scores for the pain, planning, intimate relationship, burden to others, emotional health, and fatigue domains also improved significantly (p<0.05). CONCLUSIONS: The overall outcomes showed promising results of improved self-care knowledge, health behaviors, mental health status, and quality of life. It is recommended that the SLE Foundation continues to use the eWP model to help the lupus patient community.

A smartphone-based supportive counseling on health anxiety and acceptance of disability in Systemic Lupus Erythematosus patients: A randomized clinical trial.

OBJECTIVE: This study aimed to evaluate the effects of a supportive counseling via the smart phone on the health anxiety, and acceptance of disability in the patients with Systemic Lupus Erythematosus. METHODS: The present study was a randomized clinical trial with pre-post design. Randomly dividing 124 patients into experimental and control groups. Before and after the intervention, all patients answered the health anxiety and disability acceptance questionnaires. For eight weeks, the trial group received remote counseling help using the WhatsApp platform. RESULTS: All 124 patients randomized into groups, completed follow-up which were analyzed. By the end of 8th week, the level of health anxiety (MD=11.34, P < 0.001) of the experiment group was significantly lower than the control group, while the level of acceptance of disability (MD=91.42, P < 0.001) of experiment group was significantly higher than the control group. CONCLUSION: Smartphone-based supportive counseling may help people with Systemic Lupus Erythematosus manage their symptoms better, and live better by reducing health worry and increasing acceptance of impairment. PRACTICE IMPLICATIONS: Virtual supportive counseling can assist healthcare professionals to optimize the potential of education and support processes.

Psychological Implications to the Therapy of Systemic Lupus Erythematosus.

Systemic lupus erythematosus (SLE) is a chronic and multi-systemic autoimmune disease, which has a deleterious impact on patients' psychological well-being. This paper aims to review the existing literature on empirical research on psychological outcomes of SLE and psychological interventions to improve well-being in SLE patients. A search of significant English language articles was conducted in PubMed, Medline, ScienceDirect, Scopus, and ResearchGate databases. Titles and abstracts were screened for the relevant terms, including "systemic lupus erythematosus", "childhood-onset systemic lupus erythematosus", "juvenile systemic lupus erythematosus", "lupus nephritis", and their respective synonyms along with "depression", "anxiety", "fatigue", "medical adherence", "health-related quality of life", "self-management" or "intervention". The articles were evaluated by independent reviewers and the lists of eligible publications were compared whilst disagreements were settled by discussion. Of the 59 publications sought for retrieval, 35 papers were shortlisted based on predefined inclusion/exclusion criteria. They were classified according to their content and the methodology applied. Research topics including "anxiety and depression in SLE" and "self-management interventions for SLE patients" were identified and are presented in this review. As the prognosis and life expectancy of SLE patients are improving, further research on the psychological outcomes of SLE and the evidence-based psychological interventions to improve patients' well-being are justified.

Dendritic cells in systemic lupus erythematosus: From pathogenesis to therapeutic applications.

Systemic lupus erythematosus (SLE) is a severe chronic systemic autoimmune disease caused by complicated interactions among genetic, epigenetic, and immunological factors. Dendritic cells (DCs), as the most important antigen-presenting cells, play pivotal roles in both triggering pathogenic autoimmune responses, and also maintaining immune tolerance. Distinct DC subsets are endowed with diversified phenotypic and functional characteristics, and play variable roles in shaping immunity and tolerance during the development of SLE. Abnormal activation or disabled tolerance of DCs not only triggers aberrant production of inflammatory mediators and type I interferons leading to pathogenic innate immunity and autoinflammation, but also causes an imbalance of effector versus regulatory T cell responses and sustained production of auto-antibodies from B cells, leading to continuously amplified autoimmune pathogenesis in SLE. Over the past decade, significant progress has been made in revealing the changes of DC accumulation or function in SLE, and how the functional dysregulations of DCs contribute to the pathological inflammation of SLE, leading to breakthroughs in DC-based therapeutics in the treatment of SLE. In this review, we review the recent advances in the activation and function of the major DC subsets in the pathogenesis of SLE as well as the therapeutic potential of targeting DC subset or status against SLE.

A case report of pediatric systemic lupus erythematosus with diffuse alveolar hemorrhage following COVID-19 infection: Causation, association, or chance?

RATIONALE: Diffuse alveolar hemorrhage (DAH) is a rare manifestation of childhood systemic lupus erythematosus (SLE) that can be life-threatening. Several reports have linked previous or concurrent coronavirus disease (COVID-19) infections with a high prevalence of autoimmune and autoinflammatory disorders. PATIENT CONCERNS: We report a case of a 13-year-old female who presented with DAH due to SLE 2 months after a laboratory-confirmed severe COVID-19 infection. DIAGNOSES: The patient was diagnosed with DAH due to SLE 2 months after a laboratory-confirmed severe COVID-19 infection. INTERVENTIONS AND OUTCOMES: The patient was treated with intravenous methylprednisolone pulse, broad-spectrum antibiotics, and supportive measures. In addition, she received 6 sessions of plasma exchange and maintenance methylprednisolone therapy (2 mg/kg/day). The patient then improved and was discharged on prednisolone, hydroxychloroquine, and azathioprine. LESSONS: We suggest plasmapheresis be considered a treatment for SLE-associated DAH in the context of active disease when conventional treatment has failed to induce a rapid response. In addition, further studies are needed to assess the role of COVID-19 as an autoimmune disease trigger, particularly for SLE.

Systemic lupus erythematosus: overview, management and COVID-19.

Systemic lupus erythematosus is a complex multi-system disease affecting various systems of the body. The aetiology remains unclear; however, it is thought that immune system dysregulation, environmental factors and viral susceptibility can trigger the disease. Mortality remains high due to cardiovascular disease, infection and lupus nephritis. Clinical assessment should comprise an extensive history, detailed physical examination and relevant laboratory tests. Management begins with an in-depth understanding of disease-specific complications and associated comorbidities. Treatments should be based on a shared decision-making process between the patient and the clinician. Review by a specialist nurse is vital for ongoing support and education. Current treatments can increase the risk of COVID-19 infection and disease severity, so caution is needed in the current climate. New treatments are emerging and offer hope to those with refractory disease.

A home-based exercise program during COVID-19 pandemic: Perceptions and acceptability of juvenile systemic lupus erythematosus and juvenile idiopathic arthritis adolescents.

OBJECTIVES: To investigate the perceptions and acceptability of a home-based exercise intervention in systemic lupus erythematosus (JSLE) and juvenile idiopathic arthritis (JIA) adolescent patients during the COVID-19 pandemic, and to explore the effects of the intervention on health-related quality of life (HRQoL), sleep quality, and mental health conditions parameters. METHODS: This was a randomized controlled trial of a 12-week, home-based exercise training program conducted between October and December 2020. During this period, social distancing measures were in place in Brazil to contain the spread of COVID-19. Adolescent patients diagnosed with JSLE and JIA participated in the study. Health-related qualitative and quantitative data were collected before and after the follow-up. RESULTS: 21 JSLE patients and 30 JIA patients were analyzed. Six themes emerged from patients' feedback: 1) Suitability of the home-based format; 2) Appropriate trainer supervision, 3) Motivators and facilitators for the program; 4) Barriers to the program; 5) Health benefits; 6) Patients' suggestions to improve the program. Overall, data indicated that the intervention showed good acceptability and elicited improvements in the perceived HRQoL and fatigue in JIA and JSLE patients during the pandemic. However, further quantitative analyses with validated HRQoL, sleep quality, and mental health conditions instruments did not capture these benefits (p>0.05). CONCLUSION: Our main findings based on in-depth qualitative assessments suggest that a home-based exercise training program was suitable and well-accepted by adolescents with JSLE and JIA during the COVID-19 pandemic. Nonetheless, adherence was not high, particularly among JIA patients, suggesting that facilitators and barriers identified in the current study should be explored to improve the quality of new home-based exercise programs implementation, particularly in a future emerging crisis.

Use of telemedicine for follow-up of lupus nephritis in the COVID-19 outbreak: The 6-month results of a randomized controlled trial.

OBJECTIVE: This study aimed to evaluate the short-term patient satisfaction, compliance, disease control, and infection risk of telemedicine (TM) compared with standard in-person follow-up (FU) for patients with lupus nephritis (LN) during the COVID-19 pandemic. METHOD: This was a single-center open-label randomized controlled study. Consecutive patients followed at the LN clinic were randomized to either TM or standard FU (SF) group in a 1:1 ratio. Patients in the TM group received FU via videoconferencing. SF group patients continued conventional in-person outpatient care. The 6-month data were compared and presented. RESULTS: From June to December 2020, 122 patients were randomized (TM: 60, SF: 62) and had at least 2 FUs. There were no baseline differences, including SLEDAI-2k and proportion of patients in lupus low disease activity state (LLDAS), between the two groups except a higher physician global assessment score (PGA) in the TM group. After a mean FU of 19.8 ± 4.5 weeks, the overall patient satisfaction score was higher in the TM group. More patients in the TM group had hospitalization (15/60, 25.0% vs 7/62, 11.3%; p = .049) with higher baseline PGA (OR = 1.17; 95% CI, 1.08-1.26) being the independent predictor. The proportions of patients remained in LLDAS were similar in the two groups (TM: 75.0% vs SF: 74.2%, p = .919). None of the patients had COVID-19. CONCLUSIONS: TM FU resulted in better patient satisfaction and similar short-term disease control in patients with LN compared to standard care. However, it was associated with more hospitalizations and might need to be complemented by in-person visits especially in patients with higher PGA.

Telemedicine in rheumatology: high specificity and sensitivity of follow-up virtual video consultations during COVID-19 pandemic.

OBJECTIVE: To evaluate the reliability of virtual video-assisted visits, added to the tight-control strategy for inflammatory rheumatic diseases (IRDs), in identifying patients who need treatment adjustment. METHODS: Tightly followed-up adult patients with RA, PsA, AS or SLE took part in a video consultation during COVID19 lockdown and repeated the same rheumatology evaluations through a face-to-face visit within 2 weeks. The sensitivity and specificity of the virtual visits for treatment decisions (categorized as: unchanged, adjusted/escalated, tapered/discontinued, need for further examinations), and the intraclass correlation coefficient (ICC) for virtually measured disease activity and patient-reported outcomes (PROs) were calculated with 95% CIs using face-to-face visits as the reference method. RESULTS: In 89 out of 106 patients (84.0%), face-to-face visits confirmed the remotely delivered treatment decision. Video-visiting showed excellent sensitivity (94.1% with 95% CI: 71.3%, 99.9%) and specificity (96.7%; 95% CI: 90.8%, 99.3%) in identifying the need for treatment adjustment due to inadequate disease control. The major driver for the low sensitivity of virtual video consultation (55.6%; 95% CI: 21.2%, 86.3%) in identifying the need for treatment tapering was SLE diagnosis [odds ratio (OR) 10.0; 95% CI: 3.1, 32.3; P <0.001], mostly because of discordance with face-to-face consultation in glucocorticoid tapering. Remotely evaluated PROs showed high reliability (ICC range 0.80-0.95), while disease activity measures had less consistent data (ICC range 0.50-0.95), especially for those diseases requiring more extensive physical examination, such as in SLE and PsA. CONCLUSION: Video-visiting proved to have high reliability in identifying the need for treatment adjustment and might support the IRDs standard tight-control strategy.

Suitability for e-health of non-pharmacological interventions in connective tissue diseases: scoping review with a descriptive analysis.

OBJECTIVE: Non-pharmacological interventions support patients with connective tissue diseases to better cope with and self-manage their diseases. This study aimed to map existing evidence on non-pharmacological interventions in patients with systemic lupus erythematosus (SLE), systemic sclerosis (SSc) and mixed connective tissue diseases regarding content, feasibility and potential suitability in an e-health setting. METHODS: A literature search was performed in eight different databases in July 2020. The intervention's content was extracted using the 'Better reporting of interventions: template for intervention description and replication (TIDieR) checklist and guide'. A Sankey diagram and descriptive statistics were used to analyse the data and illustrate the relationships between the interventions. RESULTS: Of 8198 identified records, 119 papers were eligible. One hundred and four of them (87.4%) were conducted between 2000 and 2020, mainly in the USA (SLE n=24 (21.2%), SSc n=16 (14.2%)), Brazil (SLE n=8 (7.1%), SSc n=5 (4.4%)) and Italy (SLE n=0 (0%), SSc n=12 (10.6%)). Fifty-two studies (SLE n=24 (21.2%), SSc n=28 (24.8%)) used multicomponent interventions. The single interventions were physical exercises (SLE n=16 (14.2%), SSc n=17 (15.0%)), coaching/counselling (SLE n=11 (18.0%), SSc n=0 (0%)) and education (SLE n=2 (1.8%), SSc n=3 (2.7%)). Primary outcomes focused on physical function (SLE n=1 (0.9%), SSc n=15 (13.3%)), mouth opening in SSc (n=4 (5.9%)) and physical capacity (SLE n=2 (1.8%), SSc n=1 (0.9%)). No interventions for mixed connective tissue disease were found. CONCLUSION: There was a great variety in the intervention's content due to differences in body structure, activity limitations and participation restrictions in SLE and SSc. These results highlight the need for personalised, multicomponent, non-pharmacological interventions, which could be delivered as e-health interventions.

Mesenchymal stem cells: ideal seeds for treating diseases.

Mesenchymal stem cells (MSCs), a kind of multipotent stem cells with self-renewal ability and multi-differentiation ability, have become the "practical stem cells" for the treatment of diseases. MSCs have immunomodulatory properties and can be used to treat autoimmune diseases, such as systemic lupus erythematosus (SLE) and Crohn's disease. MSCs also can be used in cancer and aging. At present, many clinical experiments are using MSCs. MSCs can reduce the occurrence of inflammation and apoptosis of tissue cells, and promote the proliferation of endogenous tissue and organ cells, so as to achieve the effect of repairing tissue and organs. MSCs presumably also play an important role in Corona Virus Disease 2019 (COVID-19) infection.

Systemic lupus erythematosus and COVID-19 during pregnancy.

Background: The ongoing corona virus disease 2019 (COVID-19) pandemic is having a worldwide impact. Valuable information on the clinical characteristics of COVID-19 in pregnant patients with an autoimmune disease, such as systemic lupus erythematosus (SLE), is currently lacking. Methods: Herein, we describe the clinical presentation of 2 pregnant patients with SLE and mild symptomatic COVID-19 infection. Results: In both pregnant SLE patients, a watchful-waiting approach without initiation of treatment for COVID-19 was taken. No adverse outcomes were reported and both pregnancies resulted in healthy neonates born at term. In one patient we observed a flare in SLE disease activity, most likely attributed to discontinuing SLE treatment. Conclusion: Our report highlights the importance of multidisciplinary collaboration between health care professionals as well as individualized treatment decisions during unprecedented periods such as the current COVID-19 pandemic. Discontinuation of immunosuppressive drugs during the acute phase of a COVID-19 infection should be considered on a case-by-case basis. Maternal treatment decisions should be in line with current recommendations for treatment of rheumatic and musculoskeletal diseases during COVID-19 infection and in line with treatment of COVID- 19 during pregnancy.

Neutrophil Extracellular Traps in Inflammatory Bowel Disease: Pathogenic Mechanisms and Clinical Translation.

The Inflammatory Bowel Diseases (IBD), Ulcerative Colitis (UC) and Crohn's Disease (CD) are characterised by chronic non-resolving gut mucosal inflammation involving innate and adaptive immune responses. Neutrophils, usually regarded as first responders in inflammation, are a key presence in the gut mucosal inflammatory milieu in IBD. Here, we review the role of neutrophil extracellular trap (NET) formation as a potential effector disease mechanism. NETs are extracellular webs of chromatin, microbicidal proteins and oxidative enzymes that are released by neutrophils to contain pathogens. NETs contribute to the pathogenesis of several immune-mediated diseases such as systemic lupus erythematosus and rheumatoid arthritis; and recently, as a major tissue damaging process involved in the host response to severe acute respiratory syndrome coronavirus 2 infection. NETs are pertinent as a defence mechanism at the gut mucosal interphase exposed to high levels of bacteria, viruses and fungi. On the other hand, NETs can also potentiate and perpetuate gut inflammation. In this review, we discuss the broad protective vs. pathogenic roles of NETs, explanatory factors that could lead to an increase in NET formation in IBD and how NETs may contribute to gut inflammation and IBD-related complications. Finally, we summarise therapeutic opportunities to target NETs in IBD.

Sexual dimorphism in immunometabolism and autoimmunity: Impact on personalized medicine.

Immune cells play essential roles in metabolic homeostasis and thus, undergo analogous changes in normal physiology (e.g., puberty and pregnancy) and in various metabolic and immune diseases. An essential component of this close relationship between the two is sex differences. Many autoimmune diseases, such as systemic lupus erythematous and multiple sclerosis, feature strikingly increased prevalence in females, whereas in contrast, infectious diseases, such as Ebola and Middle East Respiratory Syndrome, affect more men than women. Therefore, there are fundamental aspects of metabolic homeostasis and immune functions that are regulated differently in males and females. This can be observed in sex hormone-immune interaction where androgens, such as testosterone, have shown immunosuppressive effects whilst estrogen is on the opposite side of the spectrum with immunoenhancing facilitation of mechanisms. In addition, the two sexes exhibit significant differences in metabolic regulation, with estrous cycles in females known to induce variability in traits and more pronounced metabolic disease phenotype exhibited by males. It is likely that these differences underlie both the development of metabolic and autoimmune diseases and the response to current treatment options. Sexual dimorphism in immunometabolism has emerged to become an area of intense research, aiming to uncover sex-biased effector molecules in the various metabolic tissues and immune cell types, identify sex-biased cell-type-specific functions of common effector molecules, and understand whether the sex differences in metabolic and immune functions influence each other during autoimmune pathogenesis. In this review, we will summarize recent findings that address these critical questions of sexual dimorphism in immunometabolism as well as their translational implications for the clinical management of autoimmune diseases.

COVID-19 in systemic lupus erythematosus: Data from a survey on 417 patients.

BACKGROUND: Systemic lupus erythematosus (SLE) is a chronic disease characterised by autoimmunity and increased susceptibility to infections. COVID-19 is a systemic viral disease currently spreading as a pandemic. Little is known about the impact of COVID-19 in patients with SLE. OBJECTIVE: to acquire information on the impact of COVID-19 in SLE. METHODS: A 26-item anonymous questionnaire investigating demographics, SLE clinical features, COVID-19 diagnoses and changes in treatments and daily habits was administered to patients with SLE from three referral centres through www.surveymonkey.com over 10 days. Data from the survey were compared to those from published estimates about the general population. RESULTS: Four-hundred-seventeen patients responded to the survey. More than 60% of subjects complained of symptoms that are also associated to COVID-19. Fourteen COVID-19 diagnoses (five confirmed by polymerase chain reaction) were reported, in contrast to a 0.73% prevalence of confirmed cases in Lombardy. One hospitalisation was reported. Fever, anosmia, dry cough, a self-reported history of neuropsychiatric SLE and a recent contact with confirmed COVID-19 cases were more strongly associated with COVID-19, as were symptoms and lower compliance to behavioural preventive measures in patients' contacts. No protective effect was seen in subjects on hydroxychloroquine. CONCLUSION: COVID-19 morbidity might only moderately be increased in most patients with SLE, although limited information can be inferred on more severe cases. Hydroxychloroquine apparently seems not to confer protection to infection per se, although other beneficial roles cannot be excluded. Containment policies and behavioural preventive measures could have a major role in limiting the impact of COVID-19 in patients with SLE.