Disease-Modifying Drugs for Adult-Onset Rheumatoid Arthritis.

This article summarizes a 2022 clinical practice guideline on the use of disease-modifying antirheumatic drugs (DMARDs) for adults with rheumatoid arthritis from the European League Against Rheumatism (EULAR).

Immune Checkpoint Inhibitors and Lupus Erythematosus.

Immune checkpoint inhibitors (ICIs) are the standard of care for a growing number of malignancies. Unfortunately, they are associated with a broad range of unique toxicities that mimic the presentations of primary autoimmune conditions. These adverse events are termed immune-related adverse events (irAEs), of which ICI-lupus erythematosus (ICI-LE) constitutes a small percentage. Our review aims to describe the available literature on ICI-LE and ICI treatment for patients with pre-existing lupus. Most diagnoses of ICI-LE had findings of only cutaneous lupus; four diagnoses of ICI-LE had systemic lupus manifestations. Over 90% (27 of 29) of cases received anti-PD-1/PDL-1 monotherapy, 1 received combination therapy, and 1 received only anti-CTLA-4 treatment. About three-fourths (22 of 29 or 76%) of patients with ICI-lupus were managed with topical steroids, 13 (45%) received hydroxychloroquine, and 10 (34%) required oral corticosteroids. In our case series, none of the patients with pre-existing lupus receiving ICI therapy for cancer had a flare of their lupus, but few had de novo irAE manifestations, all of which were characterized as low-grade. The review of the literature yielded seven ICI-LE flares from a total of 27 patients with pre-existing lupus who received ICI. Most flares were manageable without need for ICI cessation.

OMERACT 2023 Systemic Lupus Erythematosus Special Interest Group: Winnowing and Binning Preliminary Candidate Domains for the Core Outcome Set.

BACKGROUND: The Outcome Measures in Rheumatology (OMERACT) Systemic Lupus Erythematosus (SLE) Working Group held a Special Interest Group (SIG) at the OMERACT 2023 conference in Colorado Springs where SLE collaborators reviewed domain sub-themes generated through qualitative research and literature review. OBJECTIVE: The objective of the SIG and the subsequent meetings of the SLE Working Group was to begin the winnowing and binning of candidate domain sub-themes into a preliminary list of candidate domains that will proceed to the consensus Delphi exercise for the SLE COS. METHODS: Four breakout groups at the SLE SIG in Colorado Springs winnowed and binned 132 domain sub-themes into candidate domains, which was continued with a series of virtual meetings by an advisory group of SLE patient research partners (PRPs), members of the OMERACT SLE Working Group Steering Committee, and other collaborators. RESULTS: The 132 domain sub-themes were reduced to a preliminary list of 20 candidate domains based on their clinical and research relevance for clinical trials and research studies. CONCLUSION: A meaningful and substantial winnowing and binning of candidate domains for the SLE COS was achieved resulting in a preliminary list of 20 candidate domains.

Lupus mastitis and antiphospholipid syndrome treated with anticoagulation and immunosuppression: a case report.

BACKGROUND: Systemic lupus erythematosus is an autoimmune disease that can have cutaneous and systemic manifestations. Lupus panniculitis, also known as lupus mastitis, is a subset of chronic cutaneous lupus erythematosus that involves inflammation of the subcutaneous fat. The pathogenesis of lupus mastitis is not fully understood. Diagnosis involves a combination of skin manifestations, imaging, and pathologic confirmation. Treatment typically includes steroids and antimalarials, with more severe disease requiring additional immunosuppressive medications. This report highlights a case of lupus mastitis treated with rituximab and a possible relationship between this disease process and thrombotic disease. CASE PRESENTATION: A 48-year-old African American female with systemic lupus erythematosus and antiphospholipid syndrome presented with new breast lesion. Mammography revealed calcifications and increased density with coarse trabecular pattern. Breast biopsy showed features of cutaneous lupus and occlusive vasculopathy. The patient was diagnosed with lupus mastitis and treated with anticoagulation, rituximab, mycophenolate mofetil, and quinacrine with resolution of her symptoms. CONCLUSION: This patient experienced improvement in her breast symptoms with combination therapy including rituximab. There are only two other cases reported in literature of patients with lupus mastitis responding to rituximab, highlighting the possible role of B cell depleting therapy for those who have contraindications to standard treatments for lupus mastitis. While the pathophysiology of lupus mastitis is thought to be immune driven, some literature suggests that associated thrombosis commonly seen may be due to a physiologic overlap similar to antiphospholipid syndrome. The possible relationship between antiphospholipid syndrome and lupus mastitis and the use of antiplatelet and anticoagulation therapy is discussed and may warrant further investigation.

Video-polysomnographic characterization of sleep movements in children with restless sleep disorder.

STUDY OBJECTIVES: Children with "restless sleep disorder" (RSD) were previously identified clinically and polysomnographically. In this study, we attempt to characterize their sleep-related movements and describe them in terms of type of movement, duration, and timing. METHODS: Video-polysomnography (vPSG) from 15 school-aged children with RSD, 15 sex- and age-matched children with restless legs syndrome (RLS), and 15 controls was reviewed for identification of sleep-related movements. Data obtained included the routine data collected during PSG and the video assessment of the movements which included time of the night when the movement occurred, type of movement (arms, legs, and body position change), and duration of the movement. RESULTS: vPSG recordings from 15 children with RLS (12 males, 3 females) with a mean age of 11.9 (SD: 3.52), 15 participants with RSD (11 males, 4 females) with a mean age of 9.5 (SD: 3.18), and 15 controls (9 males, 6 females) with a mean age of 10. The total movement index, obtained by summing together all types of movements in each participant and dividing it by the total sleep time, was prominent in children with RSD in all sleep stages. Five movements per hour gave 100% accuracy vs. controls and 90% vs. RLS. Movements occurred all night. CONCLUSIONS: We have characterized the sleep-related movements of children with RSD in comparison to the movements in children with RLS and in controls. We identified that children with RSD move all night and an index of 5 per hour accurately separates RSD from other disorders.

Overview of pathophysiology and treatment of human lupus nephritis.

PURPOSE OF REVIEW: Despite recent developments and treatment successes, the outcome, and prognosis of patients with lupus nephritis (LuN) have not greatly changed since the 1980s. This review covers the application of new concepts to the understanding of renal inflammation and the study of new pharmacologic agents to improve patient outcomes. RECENT FINDINGS: Studies have shown that the presence of anti-vimentin antibodies and T follicular helper cells in patient biopsies is associated with more severe interstitial inflammation, which has been tied to faster disease progression and onset of end-stage renal disease. Additionally, data regarding the role of serum IgE antidouble-stranded DNA antibodies in LuN by means of mediating IFN1 production by plasmacytoid dendritic cells are highlighted. Finally, a thorough review of completed and currently open clinical trials of therapeutic agents is provided. SUMMARY: Current management of LuN is guided almost exclusively by glomerular involvement. Based on the data provided in this review, we argue that renal tubulointerstitial inflammation is no less important and represents an overlooked feature in the current clinical approach to patients. Tubulointerstitial inflammation is driven by both adaptive and innate immune mechanisms that are still poorly understood. Studying these pathogenic processes promises to reveal new therapeutic opportunities for those LuN patients with the worst prognosis. VIDEO ABSTRACT: Alternate video abstract introduction (see Video, Supplemental Digital Content 1, with introduction by two of the authors - VL and KT). Abstract Video: http://links.lww.com/COR/A35.

The Pathogenesis and Therapeutic Implications of Tubulointerstitial Inflammation in Human Lupus Nephritis.

Nephritis is a common complication of systemic lupus erythematosus for which current therapies often prove inadequate. Current lupus nephritis classification systems emphasize glomerular acuity and scarring. However, tubulointerstitial inflammation (TII) and scarring are much better predictors of progression to renal failure. It now is becoming clear that the immunologic features, and probable underlying mechanisms, are very different in lupus glomerulonephritis and TII at the time of biopsy. Although glomerulonephritis is a manifestation of systemic autoimmunity, TII is associated with local in situ adaptive immune cell networks predicted to amplify local inflammation and tissue damage. In addition, poorly defined networks of innate immune cells and effectors likely contribute to the severity of local inflammation. Defining these in situ immune mechanisms should lead to a better understanding of prognostically meaningful lupus nephritis subsets and show novel therapeutic opportunities.