Diagnosis of dermatomyositis: Autoantibody profile and muscle pathology

Abstract

Dermatomyositis (DM) is an idiopathic inflammatory myopathy, which not only affects skeletal muscle and skin, but it is also associated with arthritis/ arthralgia, interstitial lung disease and cancer. The diagnostic criteria for myositis that Bohan and Peter formulated in 1975, which are often still used now, depend on the presence of a characteristic skin rash for classification of DM; without it, a diagnosis of polymyositis is given. However, advances in understanding the etiology of idiopathic inflammatory myopathies over the past few decades are impressive, encompassing discovery of myositisspecific/associated autoantibodies and development of muscle pathology, and enable us to classify them more precisely based on the underlying etiology. Correlations between clinical phenotypes and DM-specific autoantibodies (anti-Mi-2, TIF-1, NXP2, MDA5 and SAE) have been mostly elucidated, suggesting the diagnostic utility of autoantibody measurement. Advances in muscle pathology include analysis at the molecular level, such as the detection of myxovirus resistance protein A in myofibers, which can be used as a sensitive and specific pathological marker of DM. Today, a multidisciplinary approachautoantibody profiling and pathological assessment, as well as clinical evaluationis cardinal for a diagnosis of DM. The present review consolidates current knowledge about autoantibodies and muscle pathology in terms of diagnostic practice of DM.

Clinical practice guidance for juvenile dermatomyositis (JDM) 2018-Update

“…Histopathological studies have revealed ischemic change due to inflammatory or non-inflammatory systemic vasculopathy, and both apoptosis of the muscle cells and amplification of inflammation mediated by type-I interferon (IFN) in JDM [1,5,12]. Pathological roles of macrophages, T cells, plasmacytoid dendritic cells (pDCs), and autoantibodies have been suggested in the development of inflammatory myositis.…”

Diagnostic potential of sarcoplasmic myxovirus resistance protein A expression in subsets of dermatomyositis

“…The sensitivity and specificity for overall DM patients (respective 77% and 100%) were consistent with those in the previous study using a different cohort which revealed 71% of sensitivity and 98% of specificity , further corroborating its high potential as a pathological marker for DM. Although pathological changes of DM are generally conspicuous in perifascicular areas , myofibres with MxA overexpression were seen beyond perifascicular regions in nearly half of the DM samples positive for sarcoplasmic MxA expression, representing the value of MxA immunostaining to increase diagnostic sensitivity and accuracy. Practically, improvement of pathological diagnosis for DM without PFA is particularly important.…”

“…ASS is associated with anti‐aminoacyl transfer RNA synthetase autoantibodies and clinically with myositis, characteristic skin lesion (mechanic's hands are typical, but heliotrope rash and Gottron's signs/papules can also be seen), Raynaud phenomenon, interstitial lung disease, arthritis/arthralgia, and systemic symptom such as fever . Some of the clinical features and a pathological finding of perifascicular reinforcement of human leucocyte antigen (HLA)‐ABC [major histocompatibility complex (MHC) class I] expression on the sarcoplasm are shared with DM, yet ASS has a unique myopathological phenotype.…”

“…A diagnosis of dermatomyositis (DM) is achieved multidisciplinarily by clinical evaluation, autoantibody measurement in sera and morphological analysis of skeletal muscle . Muscle biopsy plays an important role to validate and complement clinical and serological diagnosis, and to diagnose clinically atypical or seronegative patients.…”

“…Perifascicular atrophy (PFA; a cluster of atrophic myofibres in the perifascicular region) has been held as a gold standard item to so‐called ‘definite diagnosis’ of DM in many classification schemes . However, the sensitivity of PFA is limited, mainly because muscle biopsy samples of DM patients may not always include PFA due to its patchy distribution or due to poorly affected biopsy site . Also, PFA or PFA‐like lesions can be seen in antisynthetase syndrome (ASS) .…”