Canadian Rheumatology Today

Capillaroscopy in Systemic Autoimmune Rheumatic Diseases: A Clinical Tool Linking Diagnosis and Pathogenesis

2025-06-09T13:41:41+00:00

Systemic autoimmune rheumatic diseases (SARDs) including systemic lupus erythematosus (SLE), systemic sclerosis (SSc), and idiopathic inflammatory myopathies (IIMs) are multisystemic, potentially life-threatening autoimmune diseases. These diseases are associated with the highest frequency of disease-associated morbidity and mortality among rheumatic diseases, largely because their complex pathophysiology remains poorly and incompletely understood. Mortality in SARDs is associated with profound vascular dysfunction ranging from cardiovascular disease to more discreet localized vascular complications including Raynaud’s phenomenon (RP), digital ulcers, and pulmonary arterial hypertension (PAH). These vascular complications stem from damage to endothelial cells caused by immune complex deposition, platelet activation, autoantibodies that promote thrombosis (e.g., antiphospholipid antibodies), and immune dysregulation.

The relationship between endothelial cell dysfunction and SARDs was first recognized by Maurice Raynaud in the 19th-century, particularly in the context of localized digital ischemia and gangrene. RP is a frequently-encountered problem in clinical practice, with a prevalence in the general population ranging from approximately 5–18%. While most cases of RP are not associated with SARDs, patients with SARDs commonly experience RP. This underscores the importance of vasculopathy related to endothelial dysfunction in the pathogenesis of SARDs.

RP is often the earliest presenting feature in up to 20% of patients with SARDs. Indeed, greater than 95% of patients with SSc experience RP.¹¹ Patients with SLE, IIMs including anti‑synthetase syndrome (ASyS), and Sjögren’s disease are also commonly affected. Hence, a closer evaluation for microvascular changes is paramount in the clinical assessment of patients with SARDs. This article will review how nailfold video capillaroscopy is emerging as a valuable point-of-care tool for diagnosis and risk stratification by providing a window into the underlying endothelial dysfunction observed in these conditions.

Glucagon-like-peptide 1 (GLP-1) Receptor Agonists in Rheumatologic Disease

2025-06-09T13:41:40+00:00

Obesity is a complex chronic disease that increases the risk of long-term medical complications and reduces lifespan due to excess body fat or adiposopathy. As of 2016, obesity affects 8.3 million (26.4%) of the Canadian population. Severe obesity, defined as a body mass index (BMI) >35 kg/m², affects an estimated 1.9 million Canadians. The financial burden of obesity, including both direct and indirect costs, was estimated to be $7.1 billion in 2010. The pathophysiology of obesity is complex and involves a combination of genetic, metabolic, behavioural, and environmental factors. The hypothalamus regulates appetite and energy expenditure, while the mesolimbic area controls the emotional, pleasurable, and rewarding aspects of eating. The cognitive lobe is responsible for overriding the hedonic drive of the mesolimbic system. Adipose tissue itself contributes to its regulation through the release of leptin in proportion to fat mass. Leptin binds to receptors in the hypothalamus to reduce appetite and increase energy expenditure. Similarly, insulin binds to receptors in the arcuate nucleus of the hypothalamus also reducing appetite and increasing energy expenditure.

The Past, Present and Future of Antinuclear Antibody (ANA) Testing

2025-06-09T13:41:39+00:00

This article is in memory of Dr. Eng M. Tan (Emeritus: The Scripps Research Institute) and acknowledges the remarkable mentorship and tremendous contributions to our understanding of
anti-nuclear antibodies (ANA). Dr. Tan passed away in 2024 at the age of 97.

More than 70 years have passed since the discovery of the lupus erythematosus (LE) cell and the development of the LE cell test, which led to the ‘tipping point’ for the discovery of antinuclear antibody (ANA), or what should more correctly be referred to as anti-cellular antibodies (ACA). Paralleling the evolution of ANA testing based on the indirect immunofluorescence assay (IFA) on cryopreserved organ sections in the 1960s and through the early 1970s was an ‘explosion’ in the spectrum of ANA and a remarkable transition in technologies used to detect ANA. This included the transition to IFA on HEp-2 cell substrates beginning in the late 1970s. While some of the ‘octogenarian’ immunoassays such as double immunodiffusion, hemagglutination, complement fixation, radioimmunoassay, and counterimmunoelectrophoresis are fading into oblivion, the ANA IFA has prevailed because of its world-wide use as a screening test for systemic autoimmune rheumatic diseases (SARD), diagnostic criteria for autoimmune hepatitis, a risk factor for the development of uveitis in juvenile idiopathic arthritis, and the entry criterion for classification of systemic lupus erythematosus (SLE). ANA testing, once regarded the domain of rheumatologists and clinical immunologists, has witnessed a widening spectrum of clinicians using these tests because of its links to a growing spectrum of autoimmune and autoinflammatory conditions. All of this is set against the background of remarkable advances in autoantibody detection, especially the emergence of newer high-throughput (i.e., faster turn-around‑time for results), multi-analyte array technologies (MAAT). These technologies use comparatively small serum or plasma volumes and provide higher specificity while detecting a broad range of SARD autoantibodies.

The Impact of Chimeric Antigen Receptor (CAR) T Cell Therapy: Its Potential to Reshape Rheumatology Practice

2025-06-09T13:41:38+00:00

In recent years, genetically modified T cell therapy, using chimeric antigen receptor (CAR)‑engineered T cells, has revolutionized the field of rheumatology. While CAR T cell therapy is approved by government agencies, including Health Canada, as a standard treatment for B cell lymphoproliferative malignancies, it has also shown remarkable efficacy in refractory cases of rheumatic diseases, including systemic lupus erythematosus, systemic sclerosis, idiopathic inflammatory myopathies, ANCA-associated vasculitis, and rheumatoid arthritis. A single infusion of CAR T cells has demonstrated the potential to induce long-term drug-free remission in most cases. This therapy achieves profound B cell depletion in both blood and tissues—an effect not typically observed with conventional antibody-based B cell-target therapies. Despite its transformative potential, several challenges remain, including questions around long-term safety, high costs, limited accessibility, and the absence of standardized guidelines, which complicate its broader application. Rheumatologists face practical uncertainties, such as determining the optimal timing for treatment, selecting suitable patients, and identifying which diseases might benefit the most from this therapy. This editorial explores the fundamental principles of CAR T cell therapy, highlights the unresolved challenges, and provides insights into how rheumatologists can optimize its use for managing rheumatic diseases. (Please note that this manuscript was written in April 2025. Given the rapid advancements and emerging evidence in this field, there may be updates by the time this article is published.)

Imaging for Diagnosis and Differential Diagnosis of Axial Spondyloarthritis

2025-06-09T13:41:37+00:00

Spondyloarthritis refers to a group of inflammatory rheumatic diseases characterized by shared clinical features, such as inflammatory involvement of the axial skeleton, a specific pattern of peripheral joint involvement (usually asymmetric mono- or oligoarthritis, predominantly involving the lower extremities), enthesitis, and dactylitis. Common extra-musculoskeletal manifestations include acute anterior uveitis, psoriasis, and inflammatory bowel disease (Crohn’s disease and ulcerative colitis).

Axial spondyloarthritis (axSpA) denotes the subset of spondyloarthritis with predominant involvement of the spine and sacroiliac joints. The term axSpA encompasses both non-radiographic disease (no definite structural damage on X-rays of the sacroiliac joints) and radiographic disease, which has historically been referred to as ankylosing spondylitis. In clinical practice, these entities represent a spectrum. axSpA may initially present without X-ray changes and in some patients, may later progress to classic ankylosing spondylitis.

In this article, we will review the approach to diagnosing (versus classifying) axSpA and examine the role of imaging modalities in diagnosing axSpA and distinguishing it from common mimics.