Clinical subsets of adult onset dermatomyositis defined by the MSA antibodies
• Anti-Mi-2 (nucleosome remodeling-deacetylase [NuRD]): seen in 10%–15% of DM patients. Patients present with acute onset of classic skin (V- and shawl-sign), periungual/cuticle overgrowth, and muscle features of DM. Not associated with malignancy or ILD. Manifestations respond very well to corticosteroids (CS) with 5YS over 90%. The autoantibody targets the chromodomain helicase DNA-binding protein, which is a part of the NuRD complex that participates in the remodeling of chromatin by deacetylating histones. Patients have a positive antinuclear antibody (ANA) with speckled pattern.
• Anti-melanoma differentiation-associated gene 5 (MDA-5) (clinically amyopathic DM [CADM]-140): seen in 5% to 10% of European/American DM patients and 10% to 50% of Asian DM patients. Patients present with ulcerations (nailfolds, over joints, oral), palmar papules, arthritis (60%), fever (60%), and rapidly progressive ILD (50%). Some patients (20%) have CADM (hence the name of the autoantibody, anti-CADM) although CPK, aldolase, and muscle MRI can be abnormal. The overall prognosis is poor depending on the response to ILD therapy. This MSA targets the melanoma differentiation-associated gene 5 protein which is a cytoplasmic RNA helicase that has an important role in the innate immune system response during RNA viral infections. ANA is negative although 30% have antibodies against SSA/Ro (52kD), which is a cytoplasmic antigen.
• Anti-TIF-1γ (p155/140): seen in 13% to 40% of DM patients who are typically aged over 60 years. It is highly associated with cancer. The sensitivity for diagnosing cancer-associated DM is up to 78% and specificity is 89%. The diagnostic odds ratio is 27, with a positive and negative predictive value of 58% and 95%, respectively. Patients usually present with classic DM rash that is frequently severe. Muscle disease may be low grade with normal CPK and elevated aldolase. The autoantibody targets TIF-1 family proteins, especially TIF-1γ. Notably TIF-1 proteins are interferon-responsive and have both positive and negative roles in carcinogenesis including p53 (tumor suppressor) regulation. Patients have a low-titer positive ANA with a speckled and homogenous pattern.
• Anti-nuclear matrix protein 2 (NXP2 or MJ, p140): seen in 2% to 17% of DM patients. Patient presents with classic DM rash. May have fingertip ulcerations. Subcutaneous calcifications common. Muscle disease is usually mild with normal CPK although muscle MRI may be abnormal (33%). In older patients, it is associated with underlying malignancy. The autoantibody targets the p140 NXP2.
• Anti-SAE (small ubiquitin-like modifier-1 activating enzyme or SUMO): seen in <8% and <3% of European and Asian DM patients, respectively. Patients present with DM rash and later get mild myositis (60%). Asian patients can get dysphagia and ILD. Rare to get other manifestations and there is no association with malignancy. The autoantibody targets the small ubiquitin-like modifier-activating enzyme.