Serum levels of IFN-β and CXCL10 may be useful biomarkers for assessing cutaneous disease activity in patients with DM and CADM. In addition, serum IL-6, IL-10, IL-18 and IFN-β were highly correlated with the occurrence of A/SIP. These cytokines may play a role in the pathogenesis of DM and CADM.

Objectives The anti-melanoma differentiation-associated gene 5 (MDA5) antibody is the main predictor of interstitial lung disease (ILD) in dermatomyositis (DM) and clinically amyopathic dermatomyositis (CADM). Nevertheless, a subset of MDA5+ patients have a favorable prognosis. We aimed to determine the possibility of using anti-MDA5 antibody isotypes and IgG subclasses for evaluating ILD risk. Methods The isotypes (IgG, IgA and IgM) of anti-MDA5 were detected in serum samples of 36 anti-MDA5+ patients with DM/CADM using enzyme-linked immunosorbent assay (ELISA). IgG subclasses of anti-MDA5 antibodies were further investigated. Laboratory findings and cumulative survival were analyzed based on the isotypes of anti-MDA5 and subclasses of anti-MDA5 IgG. Results Among the MDA5+ patients with DM/CADM, the positive rates of anti-MDA5 IgG, IgA, IgM were 100%, 97%, and 6%, respectively. The positive rates of anti-MDA5 IgG1, IgG2, IgG3, and IgG4 were 72%, 25%, 0%, and 28%, respectively. The incidence of acute interstitial pneumonia, mortality rate, and serum ferritin were significantly higher in anti-MDA5 IgG1+ patients than those in anti-MDA5 IgG1- patients with DM/CADM (P = 0.0027, 0.015, 0.0011, respectively). The sensitivity and specificity of anti-MDA5 IgG1 for predicting mortality were 100% and 41.7%, respectively. A combination of anti-MDA5 IgG1 and IgG4 for predicting mortality, yielded better specificity (87.5%). Conclusion IgA and IgG are the primary anti-MDA5 antibody isotypes. Anti-MDA5 IgG1 is the primary component of MDA5 IgG subclasses and anti-MDA5 IgG1 and IgG4 might serve as useful biomarkers for predicting mortality in DM-ILD.

Dermatomyositis (DM) is an idiopathic inflammatory myopathy primarily involving skin and muscles. Clinically amyopathic dermatomyositis (CADM), a subset of DM, presents with characteristic cutaneous manifestations without clinical evidence of myositis. Although rare, vesiculobullous eruptions could develop in DM patients. Such “bullous DM” is commonly considered a sign of internal malignancy. However, some cases with similar presentations were diagnosed as autoimmune blistering disease eventually. Herein, we reported two cases of CADM with autoimmune blisters formed. Case 1 presented with vesicles and was diagnosed with CADM initially. However, this patient developed blisters again years later and was diagnosed with “pemphigus foliaceous” (PF) accordingly. Case 2, with a history of nasopharyngeal carcinoma and CADM, developed bullous pemphigoid several days after using a heat patch on her abdomen. The association between disease occurrence and local skin damage might provide more evidence to support the “epitope spreading” hypothesis. Moreover, we reviewed related literature and discussed the differences between the two disease entities in clinical presentations, pathogenesis, therapy, and the risk of complications.

Objectives Dermatomyositis (DM) and clinically amyopathic dermatomyositis (CADM) patients with positive expression of anti-transcription intermediary factor 1-γ (anti-TIF1-γ) antibody (Ab) are characterized by distinct clinicopathological features. We aimed to determine the role of cytokine/chemokine profiles in the classification of anti-TIF1-γ positive DM/CADM patients. Methods Serum levels of 24 cytokines/chemokines were measured in 27 anti-TIF1-γ positive DM/CADM patients by a Luminex 200 system. Principal components analysis (PCA) and unsupervised hierarchical clustering were used to reduce variables and establish patient subgroups. Spearman’s correlation coefficient was calculated between cytokine/chemokine levels and disease activity markers. Results Among anti-TIF1-γ positive DM/CADM patients, two distinct patient clusters were identified. The diagnosis of CADM was more common in Cluster 1 than in Cluster 2 (58.3% vs 6.7%, p = 0.008). Skin disease activity was higher in Cluster 2 than in Cluster 1 as measured by CDASI-A (38.6 ± 10.4 vs 25.3 ± 10.0, p = 0.003). Patients within Cluster 2 exhibited significant muscle weakness (MRC ≤ 3, 33.3% vs 0.0%, p = 0.047), higher levels of anti-TIF1-γ Ab (92.4 ± 20.6 vs 66.9 ± 13.9, p = 0.001), and an increased malignancy rate (73.3% vs 25.0%, p = 0.021). Cluster 2 exhibited higher serum levels of CXCL10 (564.2 ± 258.8 vs 122.0 ± 97.8, p < 0.001), CCL2 (1136.6 ± 545.4 vs 441.6 ± 163.3, p < 0.001), Galectin-9 (38879.6 ± 20009.3 vs 12612.4 ± 6640.0, p < 0.001), IL-18 (436.1 ± 188.9 vs 243.0 ± 114.5, p = 0.003), TNF-α (9.3 ± 3.8 vs 5.6 ± 2.4, p = 0.007), and TNFRI (1385.1 ± 338.2 vs 2605.6 ± 928.5, p < 0.001) than Cluster 1. Conclusion In anti-TIF1-γ positive DM/CADM, we identified a “skin-predominant” cluster and a “hyperinflammation” cluster based on the cytokine/chemokine profiles. Cytokine/chemokine profiles in anti-TIF1-γ positive DM/CADM can identify discrete clusters of patients with different disease patterns, organ involvements, and clinical outcomes.