PROGNOSTIC FACTORS IN PATIENTS WITH ANTI-MDA5 ANTIBODY-POSITIVE DERMATOMYOSITIS: RETROSPECTIVE DATA ANALYSIS FROM TWO ITALIAN COHORTS

Introduction: Anti-melanoma differentiation-associated gene 5 antibody-positive dermatomyositis (anti-MDA5+ DM) is a subset of idiopathic inflammatory myopathies (IIM) characterized by multi-organ involvement, mainly skin and lungs, but also joints, muscles and heart. The disease shows a high prevalence of interstitial lung disease (ILD) and risk of rapidly progressive ILD (RP-ILD), the main cause of mortality. Aims of the study: This bicentric retrospective study investigated the prognostic value of demographic, clinical and immunological variables in anti-MDA5+ DM, identifying factors potentially associated with poor outcomes. Patients and methods: Clinical and serological data from 37 patients with anti-MDA5+ DM followed at Padua and Brescia Centers were analyzed. Lung involvement was assessed by symptoms, spirometry and high-resolution computed tomography (HRCT). RP-ILD was defined by worsening respiratory symptoms and/or HRCT deterioration within one month from onset. Cutaneous, muscular and articular involvement were evaluated clinically. Muscle involvement was further explored by blood tests, electromyography (EMG) and muscle magnetic resonance imaging (MRI); joint activity by X-rays and ultrasound (US). Myositis specific and associated antibodies were detected by immunoblotting (33 patients) or immunoprecipitation (4 patients); rheumatoid factor (RF) by turbidimetric immunoassay; anti-nuclear antibodies (ANA) by indirect immunofluorescence; anti-extractable nuclear antigens (anti-ENA) by fluorescence enzyme immunoassay (FEIA); anti-citrullinated peptides (anti-CCP) by ELISA. Statistical analysis was performed using SPSS. Continuous variables (age at diagnosis, ferritin, lymphocyte count) were analyzed with Student’s t-test; categorical variables (clinically relevant lymphopenia, association with cancer, anti-Ro52, anti-CCP) with Chi-square. For statistical purposes, survival through lung transplantation was equated with death. Results: Median age at diagnosis was 55 years; mean follow-up 3.8 years. Anti-Ro52 antibodies were found in 56.8% of patients, anti-PM-Scl75 and anti-CCP in 10.8%, RF in 8.1%, anti-Jo1 in 2.7%. ILD was present in 62.2%, RP-ILD in 40.5%, pneumomediastinum in 16.22%. HRCT patterns were: organizing pneumonia (OP) in 52%, non-specific interstitial pneumonia (NSIP) in 26.1%, NSIP/OP in 17.4%, usual interstitial pneumonia (UIP) in 4.3%. ICU admission occurred in 16.2%, death in 18.9% (all RP-ILD). Mortality in RP-ILD and ICU subgroups was 53.9% and 83.3%, respectively. Anti-Ro52 antibodies correlated with ILD (p=0.028). Lower lymphocyte count at diagnosis correlated with ILD (p=0.018), RP-ILD (p=0.006), ICU admission (p=0.046), and mortality (p<0.001). Clinically relevant lymphopenia (<800/μL) correlated with ICU admission (p=0.047), mortality (p=0.010) and RP-ILD (p=0.004). Higher age at diagnosis correlated with RP-ILD (p=0.044), ICU admission (p=0.033), mortality (p=0.009) and inversely with arthritis (p=0.003). Higher ferritin correlated with RP-ILD (p=0.021), ICU admission (p=0.022) and mortality (p=0.021) and inversely with cutaneous ulcers (p=0.023) and arthritis (p=0.028). Anti-CCP antibodies and cancer showed no significant associations. Conclusions: Elevated ferritin levels, lower lymphocyte count, clinically relevant lymphopenia, anti-Ro52 antibodies and older age at diagnosis emerged as potential negative prognostic markers in anti-MDA5+ DM. Given their availability and low cost, ferritin and lymphocyte count should be routinely evaluated at diagnosis and during follow-up to allow early risk stratification and guide therapy.