Dermatomyositis: Muscle Pathology According to Antibody Subtypes

ImportanceCurrent pathological criteria of dermatomyositis (DM) do not recognize different features among DM subtypes classified by dermatomyositis-specific antibodies (DMSAs). ObjectiveTo determine whether myopathological features differ among DM subtypes classified by DMSAs and whether the pathological features can be characterized by serologically defined DM subtype. DesignRetrospective review of muscle pathology slides of 256 patients diagnosed with DM from January 2009 to December 2020. SettingSingle center study in a tertiary laboratory for muscle diseases. ParticipantsA total of 256 patients whose DM diagnosis was pathologically confirmed based on the sarcoplasmic expression of myxovirus resistant protein A (MxA) were included. Of these, 249 patients were positive for one of the 5 DMSAs (seropositive patients, anti-TIF1-{gamma}=87, anti-Mi-2=40, anti-MDA5=29, anti-NXP-2=83, and anti-SAE=10), and 7 were negative for all 5 DMSAs (seronegative patients). ExposureHistochemical, enzyme histochemical, immunohistochemical staining, and ultrastructural study. Main outcomes and measuresHistological features stratified according to four pathology domains: muscle fiber, inflammatory, vascular, and connective tissue domains, and histological features of interest by histochemistry, enzyme histochemistry, and immunohistochemical study commonly used in the diagnosis of inflammatory myopathy. ResultsDMSAs significantly associated with characteristic histochemical and immunohistochemical features were as follows: anti-TIF1-{gamma} with vacuolated/punched out fibers (64.7%, P<.001) and perifascicular enhancement in HLA-ABC (75.9%, P<.001); anti-Mi-2 with prominent muscle fiber damage (score 4.8{+/-}2.1, P<.001), inflammatory cell infiltration (score 8.0{+/-}3.0, P=.002), perifascicular atrophy (67.5%, P=.02), perifascicular necrosis (52.5%, P<.001), increased perimysium alkaline phosphatase activity (70.0%, P<.001), central necrotic peripheral regenerating fibers (45.0%, P<.001), and sarcolemmal deposition of the membrane attack complex (67.5%, P<.001); anti-MDA5 with scattered/diffuse staining pattern of MxA (65.5%, P<.001) with less muscle pathology and inflammatory features; and anti-NXP2 with microinfarction (26.5%, P<.001); and anti-SAE and seronegative DM with HLA-DR expression (50.0%, P=.02 and 57.1%, P=.02 respectively). Conclusion and relevanceWe described an extensive study on serological-pathological correlation of DM primarily using MxA expression as an inclusion criterion. DMSAs was associated with distinctive myopathological features in our studied cohort, suggesting that different pathobiological mechanisms may underscore each subtype. Key pointsO_ST_ABSQuestionC_ST_ABSAre myopathological features different among dermatomyositis (DM) subtypes classified by DM-specific autoantibodies (DMSAs)? If so what are the characteristic features of each subtype? FindingsThis study enrolled 256 (249 DMSA-positive and 7 seronegative) patients whose DM diagnosis was made pathologically by confirming the expression of myxovirus resistant protein A in the sarcoplasm of muscle fibers in muscle biopsy samples. The DM subtypes classified by the positive DMSAs were associated with distinctively characteristic pathological features. MeaningDifferent pathological features suggest different pathological mechanisms may well underly each DM subtype classified by DMSA.