The Vasculopathy of Juvenile Dermatomyositis

Abstract

Juvenile dermatomyositis (JDM) is a rare autoimmune disease mainly characterized by muscle and skin involvement. Vasculopathy is considered central to the pathogenesis of the disease. The exact nature of vasculopathy is not yet understood but it is a complex process with both an inflammatory and a non-inflammatory, occlusive component. Impaired function of JDM vasculature includes immune complex deposition, altered expression of cell adhesion molecules predominantly inducing Th17 cell infiltration, and endothelial cell dysfunction. Development of vasculopathy is associated with the severe extra-muscular manifestations of JDM, such as gastrointestinal and cardiac manifestations, interstitial lung disease, ulcerative skin disease or development of calcinosis, and portends a poor prognosis. Correlation of histopathological findings, autoantibodies, and extensive diagnostic workup represent key elements to the early detection of vasculopathic features and early aggressive treatment. Monitoring of vasculopathy remains challenging due to the lack of non-invasive biomarkers. Current treatment approaches provide variable benefit, but better understanding of the essential pathogenic mechanisms should help lead to improved outcomes. Whilst acknowledging that evidence is limited, this review aims to describe the vasculopathy of JDM in the context of pathophysiology, clinical features, and treatment of disease.

Clinical factors associated with cutaneous histopathologic findings in dermatomyositis

“…The pathogenesis and prognostic significance of vasculopathy in dermatomyositis continues to be an area of active investigation. Within the juvenile dermatomyositis population, vasculopathy has been associated with a poor prognosis . Within adult dermatomyositis, vasculopathy has been associated with anti‐MDA‐5 autoantibody positive patients and clinical findings of cutaneous ulcers .…”

Juvenile Dermatomyositis and the Inflammatory Myopathies

“…8 Early in the disease course, cytokines and interferons cause a small vessel vasculitis. 9 Over time, however, inflammatory products occlude the vessels, leading to capillary destruction and surrounding tissue necrosis. 9,10 Tissue inflammation occurs throughout the body, but is most notable in the skeletal muscle and skin, giving the hallmark clinical features of proximal weakness and characteristic Keywords ► Inflammatory myopathies ► juvenile dermatomyositis ► inclusion body myositis ► immune-mediated necrotizing myopathy…”

“…25 Commonly affected areas are skin, subcutaneous tissue, and muscle of the elbows, knees, trunk, hands, and feet. 1,9,25 Calcinosis is a chronic finding in JDM, typically presenting greater than 1 year from the start of inflammation. 25 An uncommon but serious finding is vasculopathy in the gastrointestinal tract leading to ulceration, hemorrhage, or perforation.…”

Child with fever, rash, and abnormal gait

“…Possible emergent complications include intestinal perforation, 1,2 or hemorrhage from vasculitis, 3 severe diaphragmatic muscle weakness, dysphagia, and dysphonia leading to respiratory failure or aspiration. 4 Interstitial lung disease can occur and potentially be rapidly progressive, with anti-MDA-5-positive patients at increased risk.…”