Idiopathic Inflammatory Myopathies: an Update on Classification and Treatment with Special Focus on Juvenile Forms

Abstract

Juvenile inflammatory myopathies represent a heterogeneous group of rare and potentially fatal disorders of unknown aetiology, characterised by inflammation and proximal and symmetric muscle weakness. Beyond many similarities, specific clinical, laboratoristic and histopathologic features underlie different subsets with distinguishing demographic, prognostic and therapeutic peculiarities. Over time, several forms of inflammatory idiopathic myopathies have been described, including macrophagic myofascitis, immune-mediated necrozing myopathy and the spectrum of amyopathic dermatomyositis that include hypomyopathic dermatomyositis, inclusion body myositis and cancer-associated myositis occurring almost exclusively in adults. However, juvenile dermatomyositis is the most frequent in childhood, whereas polymyositis is relatively more frequent in adults. The aetiology is nowadays widely unclear; however, current theories contemplate a combination of environmental triggers, immune dysfunction and specific tissue responses involving muscle, skin and small vessels endothelium in genetically susceptible individuals. Myositis-specific autoantibodies, found almost exclusively in patients with myositis and myositis-associated autoantibodies, detectable both among patients with myositis and in subjects suffering from other autoimmune diseases, have an important clinical role because of their relation to specific clinical features, response to therapy and prognosis. The gold standard treatment for juvenile dermatomyositis is represented by corticosteroids, along with adjunctive steroid-sparing immunosuppressive therapies, which are used to counteract disease activity, prevent mortality, and reduce long-term disability. Further treatment approach such as biologic agents and autologous stem cell transplantation are emerging during the last years, in particular in patients difficult to treat and with poor prognosis. Therefore, a highly medical specialised approach is required for diagnosis and management of these conditions. This review comprehensively examines juvenile inflammatory myopathies focusing on clinical and laboratory classifications as well as on the current treatment approaches, referring in particular on biologic agents and latest therapeutic opportunities.

Pervasive inflammatory activation in patients with deficiency in very‐long‐chain acyl‐coA dehydrogenase (VLCADD)

“…The observed expression of MHC I molecules in muscle, a tissue that is normally MHC I negative, is a strong bioindicator of immune and inflammatory activation explaining the T‐cell/macrophage infiltration 65 . Whether or not muscle MHC I expression in VLCADD could be a form of a T‐cell/macrophage‐mediated autoimmune event analogous to recurrent myalgias in inflammatory myositis 66,67 will have to be examined. Plausibility of this suggestion might be inferred from the data showing identifiable and quantifiable activated phenotypes of T cells, NK cells and monocytes in blood of this patient.…”

Long-term follow-up of autologous hematopoietic stem cell transplantation for refractory juvenile dermatomyositis: a case-series study

“…Although the aetiology of JDM remains unclear, current theories propose a combination of environmental triggers, immune dysfunction and specific tissue responses as possible causes [ 14 ]. Many literatures point out that JDM is a true inflammatory small vessel vasculitis, and cytokines, such as interferons and tumor necrosis factor α, play an important role in the pathogenesis [ 1 , 15 ]. Besides, literatures showed AHSCT was safe for children [ 7 , 16 ].…”

“…Juvenile dermatomyositis (JDM) is a chronic autoimmune inflammatory disorder of unknown aetiology that mainly affects muscle and skin. The gold standard treatment for JDM is corticosteroids, along with immunomodulatory therapies, which are used to counteract disease activity, prevent mortality, and reduce long-term disability [ 1 ]. Although these medications have led to a significant improvement in prognosis, JDM management remains challenging due to the adverse effects associated with conventional therapies and the occurrence of refractory disease.…”

The role of exosome in autoimmune connective tissue disease

“…For example, the Mi-2 antigen was discovered to be a helicase involved in chromosome-mediated regulation of transcription as part of a nucleosome remodelling deacetylase multi-protein complex [26]. Interestingly, polymyositis/scleroderma (PM/Scl) antibodies are directed against an exosome complex that is composed of nine proteins and several associated proteins that play a role in RNA processing and degradation [27]. Several studies have investigated the prevalence of anti-PM/Scl antibodies in ACTD patients: anti-PM/Scl antibodies are usually found only in patients with PM, DM or systemic sclerosis (SSc), an autoimmune disease characterized by fibrosis and vasculopathy.…”