Risk Factors Associated with the Development of Thrombotic Microangiopathy in Patients with Dermatomyositis

Thrombotic microangiopathy (TMA) is an infrequent and poorly understood manifestation in dermatomyositis (DM) associated with poor outcomes and refractoriness to treatment. The aim of this study is to describe the clinical characteristics and risk factors for its development. We conducted a nested case-control study comparing patients with DM who developed TMA to those with DM without this complication. Disease activity was evaluated using the Myositis Disease Activity Assessment Tool (MDAAT), the Manual Muscle Test of eight muscle groups (MMT8), and muscle enzyme levels. A binomial logistic regression analysis was performed to identify risk factors for the development of TMA among patients with DM. All patients with TMA had DM. Patients with DM/TMA had a shorter time since disease onset (<i>p</i> = 0.033), lower levels of C3 (<i>p</i> = 0.07) and C4 (<i>p</i> = 0.046), as well as higher leukocyte (<i>p</i> = 0.044), neutrophil (<i>p</i> = 0.033), and creatine phosphokinase (CK) levels (p = 0.005). They also exhibited higher constitutional (<i>p</i> = 0.0008), pulmonary (<i>p</i> = 0.008), and muscle disease activity (<i>p</i> = 0.027). In the univariate analysis, a shorter time since disease onset (OR 0.42, <i>p</i> = 0.0042) indicated an increased risk for TMA, as did low complement levels (C3: OR 1.11, <i>p</i> = 0.01; C4: OR 1.18, <i>p</i> = 0.02) and higher constitutional (OR 2.27, <i>p</i> = 0.0014), pulmonary (OR 5.50, <i>p</i> = 0.0004), and muscle disease activity (OR 2.1, <i>p</i> = 0.003). Although elevated CK levels (OR 1.001, <i>p</i> = 0.0008) reached statistical significance, the effect size was minimal and should not be interpreted as a clinically relevant increase in risk. Confocal microscopy of muscle biopsy specimens demonstrated neutrophil extracellular traps (NETs) infiltrating muscle tissue. Patients with DM who develop TMA appear to exhibit a distinct clinical phenotype characterized by leukocytosis, neutrophilia, hypocomplementemia, shorter disease duration, and greater constitutional, pulmonary, and muscular disease activity. Although limited by the small sample size, these findings suggest a potential role of NETs in microvascular and tissue injury associated with DM-related TMA. Larger studies are warranted to validate these observations and further elucidate the underlying pathogenic mechanisms.