Scleromyositis: A distinct novel entity within the systemic sclerosis and autoimmune myositis spectrum. Implications for care and pathogenesis

Abstract

Systemic sclerosis and autoimmune myositis are both associated with decreased quality of life and increased mortality. Their prognosis and management largely depend on the disease subgroups. Indeed, systemic sclerosis is a heterogeneous disease, the two predominant forms of the disease being limited and diffuse scleroderma. Autoimmune myositis is also a heterogeneous group of myopathies that classically encompass necrotizing myopathy, antisynthetase syndrome, dermatomyositis and inclusion body myositis. Recent data revealed that an additional disease subset, denominated “scleromyositis”, should be recognized within both the systemic sclerosis and the autoimmune myositis spectrum. We performed an in-depth review of the literature with the aim of better delineating scleromyositis. Our review highlights that this concept is supported by recent clinical, serological and histopathological findings that have important implications for patient management and understanding of the disease pathophysiology. As compared with other subsets of systemic sclerosis and autoimmune myositis, scleromyositis patients can present with a characteristic pattern of muscle involvement (i.e. distribution of muscle weakness) along with multisystemic involvement, and some of these extra-muscular complications are associated with poor prognosis. Several autoantibodies have been specifically associated with scleromyositis, but they are not currently integrated in diagnostic and classification criteria for systemic sclerosis and autoimmune myositis. Finally, striking vasculopathic lesions at muscle biopsy have been shown to be hallmarks of scleromyositis, providing a strong anatomopathological substratum for the concept of scleromyositis. These findings bring new insights into the pathogenesis of scleromyositis and help to diagnose this condition, in patients with subtle SSc features and/or no autoantibodies (i.e. “seronegative” scleromyositis). No guidelines are available for the management of these patients, but recent data are showing the way towards a new therapeutic approach dedicated to these patients.

Neurological, cardiac, musculoskeletal, and renal manifestations of scleroderma along with insights into its genetics, pathophysiology, diagnostic, and therapeutic updates

“…A myriad number of antibodies are discovered that cause myositis, they are ACA, antibodies against anti‐Ku, PM/scl, anti‐U3‐RNP (fibrillarin) antibodies, anti‐RNAP III, anti‐RuvBL1/2 (pontin, reptin), anti‐scl70, anti‐PL12, anti‐PL7, anti‐SRP 47 . Patients present with muscle fatigue, the diverse intensity of pain, symmetrical proximal or distal muscle weakness along with idiopathic inflammatory myositis: altogether restricts movement of muscle as sclerosis and fibrosis are formed in underlying tissues eventually necrosis of muscle, ultimately affecting the daily quality of life (QoL) 28,48 . It further offenses cardiac and respiratory muscles leading to lethal diseases tend as myocarditis, left ventricle dysfunction, pericarditis, conduction defects, pulmonary fibrosis, decreased forced vital capacity (FVC), and PAH 33…”

“…47 Patients present with muscle fatigue, the diverse intensity of pain, symmetrical proximal or distal muscle weakness along with idiopathic inflammatory myositis: altogether restricts movement of muscle as sclerosis and fibrosis are formed in underlying tissues eventually necrosis of muscle, ultimately affecting the daily quality of life (QoL). 28,48 It further offenses cardiac and respiratory muscles leading to lethal diseases tend as myocarditis, left ventricle dysfunction, pericarditis, conduction defects, pulmonary fibrosis, decreased forced vital capacity (FVC), and PAH. 33 The prognosis of SSc myositis is fatal if cardiac or lung involvement as they cause severe functional glitches as stated above, sans organ acquaintance is not problematic to patients.…”

Myopathy in systemic sclerosis

“…Recently, predominant fibrosis or a fibrosing myopathy has gained recognition as the unique histopathological finding among patients with SSc-AM [9]. It is also well recognized that inflammatory muscle disease can occur in SSc, in the setting of overlap idiopathic inflammatory myopathy (IIM), described as ‘scleromyositis’ [10,11 ▪▪ ] or ‘myopathies and systemic sclerosis overlap syndrome’ [12]. Other causes of SSc-AM include neurogenic myopathy in the setting nervous system involvement, myopathy due to poor nutritional state (particularly among those with gastrointestinal involvement) and disuse myopathy (particularly among those with significant skin/contractures or poor reserve in the setting of cardiopulmonary disease) [4] (Fig.…”

“…The most common clinical manifestations of SSc-AM include muscle weakness and myalgia [10]. The most reported pattern of weakness is that of symmetric proximal muscle weakness [13 ▪▪ ,14].…”

Experimental myositis: an optimised version of C-protein-induced myositis

“…Inflammatory myopathies (IM) are rare autoimmune diseases which include dermatomyositis, immune-mediated necrotising myopathy, inclusion body myositis, anti-synthetase syndrome and scleromyositis (1)(2)(3). Despite their differences, these subgroups share common characteristics (4,5) including proximal weakness, increased serum creatine-kinase (CK) levels and histopathological lesions of the skeletal muscle (i.e.…”