Telerheumatology: A Narrative Review

Telemedicine (TM), the delivery of health care using telecommunication technologies, has been in use in rheumatology practice for over two decades to maximize access and optimize care. As a direct consequence of the Coronavirus disease 2019 (COVID-19) pandemic in March 2020, rheumatology practice shifted from traditional in-person encounters to TM to ensure the safety of both healthcare professionals and patients. However, there is limited literature on the acceptance, feasibility, and effectiveness of TM in the management of rheumatic diseases. Additionally, there is limited guidance on the implementation of telerheumatology (TR) for both patient care and clinical trials. Here we reviewed the most recent publications related to the application of TR, in the management of Rheumatoid Arthritis (RA) and Systemic Lupus Erythematosus (SLE), assessed the perceptions of patients and physicians on TM in rheumatology, and identified several key barriers to TR.

Nanoparticle-mediated delivery of IL-2 to T follicular helper cells protects BDF1 mice from lupus-like disease

We recently reported that poly lactic-co-glycolic acid (PLGA) nanoparticles (NPs) loaded with interleukin (IL)-2 and targeted to T cells inhibited the development of lupus-like disease in BDF1 mice by inducing functional T regulatory cells (Tregs). Here we show that the protection from disease and the extended survival of BDF1 mice provided by IL-2-loaded NPs targeted to T cells is not only due to an induction of Tregs but also contributed by an inhibition of T follicular helper (TFH) cells. These results identify a dual protective activity of IL-2 in the control of lupus autoimmunity, namely the inhibition of effector TFH cells, in addition to the previously known induction of Tregs. This newly recognized activity of IL-2 delivered by NPs can help better explain the beneficial effects of low-dose IL-2 immunotherapy in systemic lupus erythematosus (SLE), and might be considered as a new strategy to slow disease progression and improve outcomes in lupus patients.

CD8+ T regulatory cells in lupus

T regulatory cells (Tregs) have a key role in the maintenance of immune homeostasis and the regulation of immune tolerance by preventing the inflammation and suppressing the autoimmune responses. Numerical and functional deficits of these cells have been reported in systemic lupus erythematosus (SLE) patients and mouse models of SLE, where their imbalance and dysregulated activities have been reported to significantly influence the disease pathogenesis, progression and outcomes. Most studies in SLE have focused on CD4+ Tregs and it has become clear that a critical role in the control of immune tolerance after the breakdown of self-tolerance is provided by CD8+ Tregs. Here we review the role, cellular and molecular phenotypes, and mechanisms of action of CD8+ Tregs in SLE, including ways to induce these cells for immunotherapeutic modulation in SLE.

Regulation of cGAS-STING pathway - Implications for systemic lupus erythematosus

Type I interferon (IFN-I) is implicated in the pathogenesis of systemic lupus erythematosus (SLE) and the closely associated monogenic autoinflammatory disorders termed the “interferonopathies.” Recently, the cytosolic DNA sensor cyclic guanosine monophosphate-adenosine monophosphate synthase (cGAS) and its downstream signaling adaptor stimulator of interferon genes (STING) have been identified as having important, if not central, roles in driving IFN-I expression in response to self-DNA. This review highlights the many ways in which this pathway is regulated in order to prevent self-DNA recognition and underlines the importance of maintaining tight control in order to prevent autoimmune disease. We will discuss the murine and human studies that have implicated the cGAS-STING pathway as being an important contributor to breakdown in tolerance in SLE and highlight the potential therapeutic application of this knowledge for the treatment of SLE.

Long-term outcomes of patients with systemic lupus erythematosus: A Multicenter Cohort Study from CSTAR registry

Objective To study the long-term outcomes, in the context of both mortality and organ damage in patients with systemic lupus erythematosus (SLE) in the Chinese SLE Treatment and Research group (CSTAR) registry cohort. Methods Patients were enrolled from April 2009 to February 2010 and they were followed up. The demographic data, clinical manifestations, labs test results and imaging examinations, disease activity (SLEDAI-2K), damage scores (SLLIC/Damage Index [SDI]), and medications were collected. Data were censored at either the last clinic visit or telephonic interview. Survival rate was analyzed by Kaplan–Meier (KM) method. COX proportional hazard model was adopted to perform the analysis of predicting factors for mortality and organ damage. Logistic regression analysis was employed to discuss the relationship among mortality, organ damage, and flare. Results A total of 2104 patients were recruited at baseline and 1494 patients were followed up. The cumulative 1-year, 3-year, and 5-year survival rates were 98.3%, 96.9%, and 95.7%, respectively. Seventy-eight patients died during follow-up, and the main causes of death were infection (34.6%), active disease (26.9%), cardiovascular and cerebrovascular events (5.13%), and malignancy (5.13%). At entry, 247 patients presented with irreversible organ damage and it increased to 398 patients at the endpoint. The major accumulated organ damages were kidney (25.9%), musculoskeletal disease (20.2%), neuropsychiatric disease (12.2%), and pulmonary damage (10.9%). Cox regression analysis further showed that male, late disease onset, delayed diagnosis (diagnosis from disease onset >1 year), baseline organ damage, and specific organ involvements predicted for higher mortality. In addition, early disease onset was a protecting factor for organ damage, and anti-SSA was an independent predicting factor for new organ damage. Logistic regression analysis showed that flare predicted for more organ damage. Conclusion The 5-year survival rate of Chinese SLE patients has improved and is comparable to Caucasians SLE patients. Disease flare impact on prognosis is the increasing risk of damage development. Early diagnosis, prevention for flare and damage to maintain remission, may improve outcome.

A 31-year-old woman with painful black palms: Thrombosis or vasculitis?

Both of vaso-occlusive incidence of antiphospholipid syndrome (APS) or vasculitis secondary to systemic lupus erythematosus (SLE) can lead to gangrene, which requiring the urgent and appropriate therapeutic approach. However, it is sometimes difficult to achieve the differential diagnosis, especially when a tissue biopsy is difficult to obtain or is clinically contraindicated. Herein we report and discuss such a female patient who suffered rare progressive gangrene of palm skin and successfully treated with aggressive anticoagulation and immunosuppressive therapy.

Cardiovascular disease in systemic lupus erythematosus

There is a well-known increased risk for cardiovascular disease that contributes to morbidity and mortality in systemic lupus erythematosus (SLE). Major adverse cardiovascular events and subclinical atherosclerosis are both increased in this patient population. While traditional cardiac risk factors do contribute to the increased risk that is seen, lupus disease-related factors, medications, and genetic factors also impact the overall risk. SLE-specific inflammation, including oxidized lipids, cytokines, and altered immune cell subtypes all are likely to play a role in the pathogenesis of atherosclerotic plaques. Research is ongoing to identify biomarkers that can help clinicians to predict which SLE patients are at the greatest risk for cardiovascular disease (CVD). While SLE-specific treatment regimens for the prevention of cardiovascular events have not been identified, current strategies include minimization of traditional cardiac risk factors and lowering of overall lupus disease activity.

Systemic lupus erythematosus and immunodeficiency

Systemic lupus erythematosus (SLE) is a multisystem autoimmune disease caused by a combination of genetic, epigenetic, and environmental factors. Recent advances in genetic analysis coupled with better understanding of different immune regulatory and signaling pathways have revealed the complex relationship between autoimmunity, including SLE, and immunodeficiency. Furthermore, the expanding therapeutic armamentarium has led to the increasing awareness of secondary immunodeficiency in these patients. This article serves to update the current understanding of SLE and immunodeficiency by discussing the shared genetic factors and immunobiology. We also summarize the effects of immunosuppressive therapies with a focus on secondary antibody deficiency (SAD) after B-cell targeted therapies.

A Darwinian view of Behçet's disease

Behçet’s disease (BD) is a multisystem inflammatory disorder of unknown etiology, characterized by oral and genital ulceration, with other complications including eye, skin, joint, and central nervous system (CNS) lesions. Diagnosis is based on clinical findings, which may differ between patients. There is a strong genetic basis for BD; however, only a few genes have been associated with the disease across the geographical spread of BD. In this article, we discuss the history and combination of genes involved in this complex disease in relation to the geographical range and present our view that the disease has developed from a Darwinian perspective, with different gene polymorphisms that affect the same biological pathway. Moreover, these mutations individually are protective mechanisms against the disease relevant to each region, which affected both archaic and modern humans.