The detection of sarcoplasmic myxovirus resistance A expression in immunohistochemical analysis of muscle biopsy in patients suspected of having dermatomyositis may add greater sensitivity for the diagnosis when compared with conventional pathologic hallmarks of the disease, according to findings from a retrospective cohort study.

Myxovirus resistance A (MxA) is one of the type 1 interferon–inducible proteins whose overexpression is believed to play a role in the pathogenesis of dermatomyositis, and MxA expression has rarely been observed in other idiopathic inflammatory myopathies, said first author Akinori Uruha, MD, PhD, of the National Center of Neurology and Psychiatry, Tokyo, and his colleagues. They compared MxA expression in muscle biopsy samples from definite, probable, and possible dermatomyositis cases as well as other idiopathic inflammatory myopathies and other control conditions to assess its value against other muscle pathologic markers of dermatomyositis, such as the presence of perifascicular atrophy (PFA) and capillary membrane attack complex (MAC) deposition (Neurology. 2016 Dec 30. doi: 10.1212/WNL.0000000000003568).

This womean shows dermatomyositis rash on her thighs. Courtesy RegionalDerm.com
While some criteria have described PFA as the standard for pathologic definite diagnosis of dermatomyositis, Dr. Uruha and his associates noted that it has been criticized for its low sensitivity because of the inconsistency of capturing clusters of atrophic myofibers in perifascicular regions of muscle biopsy samples. They also noted that a sensitive muscle pathology marker for dermatomyositis would be helpful when patients develop skin disease years after the onset of muscle weakness, making a marker such as MxA expression a potentially important method for diagnosing the disease, at least in early stages.

The investigators studied muscle biopsy samples collected from 154 consecutive patients with idiopathic inflammatory myopathies seen from all over Japan, including 34 with dermatomyositis (10 juvenile cases), 8 with polymyositis (1 juvenile), 16 with anti–tRNA-synthetase antibody–associated myopathy (ASM); 46 with immune-mediated necrotizing myopathy (IMNM), and 50 with inclusion body myositis. The IMNM cases involved included 24 with anti–signal recognition particle (SRP) antibodies, 6 with anti–3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) antibodies, and 16 without anti-SRP, anti-HMGCR, or anti–tRNA-synthetase antibodies (3 juvenile patients). They used 51 patients with muscular dystrophy and 26 with neuropathies as controls.

Sarcoplasmic MxA expression proved to be more sensitive for a diagnosis of dermatomyositis than PFA and capillary MAC deposition (71% vs. 47% and 35%, respectively) but still had comparable specificity to those two markers (98% vs. 98% and 93%, respectively).

Of 18 cases with probable dermatomyositis, defined as typical skin rash but a lack of PFA, 8 (44%) showed sarcoplasmic MxA expression, and its sensitivity was 90% in juvenile cases overall and 63% in adult patients. Only 3 (17%) of the 18 showed capillary MAC deposition. Sarcoplasmic MxA expression occurred in all 12 patients with definite dermatomyositis, defined by the typical skin rash plus presence of PFA, whereas only 7 (58%) showed capillary MAC deposition. Among the four patients with possible dermatomyositis (PFA present but lacking typical skin rash), all showed sarcoplasmic MxA expression, compared with just two showing capillary MAC deposition.

In all other patients without definite, probable, or possible dermatomyositis, only two were positive for sarcoplasmic MxA expression (one with ASM and one with IMNM).

Dr. Uruha and his associates said that the results are “clearly demonstrating that sarcoplasmic MxA expression should be an excellent diagnostic marker of [dermatomyositis].”

The authors noted that the study was limited by the fact that they could not obtain full information about dermatomyositis-associated antibodies, and because other proteins of type 1 interferon signature are known to be upregulated in dermatomyositis, additional studies will need to determine which of the proteins is a better diagnostic marker.

The study was supported partly by an Intramural Research Grant of the National Center of Neurology and Psychiatry and grants from the Japanese Ministry of Education, Science, Sports and Culture and the Ministry of Health, Labor and Welfare of Japan. The investigators had no relevant disclosures.