Several other autoantibodies are associated with unique cutaneous phenotypes. As described, anti-MDA-5 can present with painful palmar papules or ulcerations, arthritis or alopecia. Anti-small ubiquitin-like modifier activating enzyme heterodimer (anti-SAE) is reported to manifest a dark violaceous or red rash and has been associated with pulmonary arterial hypertension, particularly in Chinese populations. Anti-Mi-2 can cause punctate perionychium hemorrhage and cuticular overgrowth. Anti-TIF1-γ, reviewed above, is associated with the ovoid palatal patch and can have psoriasis-like lesions. Anti-nuclear matrix protein 2 (anti-NXP-2) can cause severe calcinosis, associated peripheral edema or intestinal vasculopathy.9
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Explore This IssueJanuary 2020
Table 3 summarizes the cutaneous and other clinical manifestations associated with particular myositis-specific antibodies that have been reported in the literature.
Dr. Christopher-Stine has also described an even rarer antibody/phenotype association seen in the setting of inflammatory myopathies: an association between severe cardiac involvement in a subgroup of myositis patients with positive antimitochondrial antibodies (AMAs). The AMAs were checked in a few myositis patients with primary biliary cirrhosis, scleroderma overlap, or as part of transaminitis workup. She noticed that several patients with severe cardiac disease requiring implantable cardioverter-defibrillators (ICDs) or defibrillators had AMAs, which she found unusual since almost none of the other patients in the cohort required defibrillators/ICDs. Her team performed a retrospective case series looking at more than 1,000 patients who underwent myositis autoantibody testing, finding seven with positive AMAs by confirmatory enzyme-linked immunosorbent assay (ELISA). Although this is a very small cohort, the researchers found a striking clinical feature of severe cardiac involvement in the majority of the patients (~70%) including severe conduction abnormalities, arrhythmias, cardiomyopathy and myocarditis.12 These patients also often had chronic skeletal muscle disease, including muscle atrophy.
The findings are diluted when looking at the cohort as a whole, Dr. Christopher-Stine explains. “Antimitochondrial antibodies are seen in other patients, and it is only a subset who go on to develop cardiac disease, one of the highest morbidity features.” She notes the cardiomyopathy seems to be responsive to treatment with immunosuppression. “We don’t fully understand how to predict which of the positive AMA patients will go on to develop cardiac involvement.”
The improved phenotyping of myositis patients in the past decade has enabled us to better understand unique clinical associations, with implications in how we evaluate and manage idiopathic inflammatory myositis. Dr. Christopher-Stine notes inflammatory myopathies are “one of the most carefully phenotyped groups of the rheumatic diseases” and the antibody/phenotype correlations have helped improve diagnostic accuracy and changed management in unique subsets.