-
Arthritis & Rheumatology (Hoboken, N.J.) Feb 2023Idiopathic inflammatory myopathies (IIMs) comprise a heterogeneous group of rare immune-mediated disorders that primarily affect muscles but also lead to dysfunction in... (Review)
Review
Idiopathic inflammatory myopathies (IIMs) comprise a heterogeneous group of rare immune-mediated disorders that primarily affect muscles but also lead to dysfunction in other organs. Five different clinical subphenotypes of IIM have been distinguished: dermatomyositis, polymyositis, inclusion body myositis, antisynthetase syndrome, and immune-mediated necrotizing myopathy. Excess mortality and morbidity associated with IIM are largely attributed to comorbidities, particularly cancer. The risk of malignancy is not equally distributed among IIM groups and is particularly high among patients with dermatomyositis. The cancer risk peaks around 3 years on either side of the IIM diagnosis and remains elevated even 10 years after the onset of the disease. Lung, colorectal, and ovarian neoplasms typically arise before the onset of IIM, whereas melanoma, cervical, oropharyngeal, and nonmelanoma skin cancers usually develop after IIM diagnosis. Given the close temporal proximity between IIM diagnosis and the emergence of malignancy, it has been proposed that IIM could be a consequence rather than a cause of cancer, a process known as a paramalignant phenomenon. Thus, a separate group of IIMs related to paramalignant phenomenon has been distinguished, known as cancer-associated myositis (CAM). Although the relationship between IIM and cancer is widely recognized, the pathophysiology of CAM remains elusive. Given that genetic factors play a role in the development of IIM, dissection of the molecular mechanisms shared between IIM and cancer presents an opportunity to examine the role of autoimmunity in cancer development and progression. In this review, the evidence supporting the contribution of genetics to CAM will be discussed.
Topics: Humans; Dermatomyositis; Myositis; Polymyositis; Myositis, Inclusion Body; Melanoma
PubMed: 36053262
DOI: 10.1002/art.42345 -
Nature Communications Jan 2022Muscle cell death in polymyositis is induced by CD8 cytotoxic T lymphocytes. We hypothesized that the injured muscle fibers release pro-inflammatory molecules, which...
Muscle cell death in polymyositis is induced by CD8 cytotoxic T lymphocytes. We hypothesized that the injured muscle fibers release pro-inflammatory molecules, which would further accelerate CD8 cytotoxic T lymphocytes-induced muscle injury, and inhibition of the cell death of muscle fibers could be a novel therapeutic strategy to suppress both muscle injury and inflammation in polymyositis. Here, we show that the pattern of cell death of muscle fibers in polymyositis is FAS ligand-dependent necroptosis, while that of satellite cells and myoblasts is perforin 1/granzyme B-dependent apoptosis, using human muscle biopsy specimens of polymyositis patients and models of polymyositis in vitro and in vivo. Inhibition of necroptosis suppresses not only CD8 cytotoxic T lymphocytes-induced cell death of myotubes but also the release of inflammatory molecules including HMGB1. Treatment with a necroptosis inhibitor or anti-HMGB1 antibodies ameliorates myositis-induced muscle weakness as well as muscle cell death and inflammation in the muscles. Thus, targeting necroptosis in muscle cells is a promising strategy for treating polymyositis providing an alternative to current therapies directed at leukocytes.
Topics: Animals; Antibodies, Neutralizing; C-Reactive Protein; Fas Ligand Protein; Female; Gene Expression Regulation; Granzymes; HMGB1 Protein; Humans; Imidazoles; Indoles; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Muscle Fibers, Skeletal; Muscle Strength; Muscle, Skeletal; Myositis; Necroptosis; Perforin; Polymyositis; Signal Transduction; T-Lymphocytes, Cytotoxic
PubMed: 35013338
DOI: 10.1038/s41467-021-27875-4 -
Seminars in Neurology Jun 2020The inflammatory myopathies comprise disorders of immune-mediated muscle injury. The histopathology and clinical features help distinguish them. Juvenile dermatomyositis... (Review)
Review
The inflammatory myopathies comprise disorders of immune-mediated muscle injury. The histopathology and clinical features help distinguish them. Juvenile dermatomyositis (JDM) is the most common form of myositis in children and adolescents. Children with JDM present with proximal muscle weakness and characteristic rashes. The presentation is similar in children and adults, but JDM is a primary disorder and the adult form often is concerning for a paraneoplastic syndrome. Proximal muscle weakness occurs with dermatomyositis, polymyositis, and immune-mediated necrotizing myopathy, but the latter two conditions have no dermatologic findings or distinct tissue changes which set them apart from dermatomyositis. Inclusion body myositis, also included in the inflammatory myopathies, presents with more distal involvement, and microscopically exhibits identifiable rimmed vacuoles. We review key features of these disorders, focusing in more detail on JDM because it is more often encountered by the child neurologist.
Topics: Adolescent; Adult; Autoimmune Diseases of the Nervous System; Child; Dermatomyositis; Humans; Inflammation; Myositis, Inclusion Body
PubMed: 32252099
DOI: 10.1055/s-0040-1705120 -
Internal Medicine Journal Apr 2020Anti-MDA5-associated dermatomyositis (MDA5-associated DM) is an uncommon presentation of idiopathic inflammatory myositis, typically amyopathic, associated with rapidly...
Anti-MDA5-associated dermatomyositis (MDA5-associated DM) is an uncommon presentation of idiopathic inflammatory myositis, typically amyopathic, associated with rapidly progressive, treatment refractory interstitial lung disease and poor prognosis, particularly in patients with concomitant rapidly progressive interstitial lung disease (RP-ILD). We report two cases of MDA5-associated DM with fatal outcome in one of the patients, despite 'aggressive triple therapy' for RP-ILD.
Topics: Autoantibodies; Dermatomyositis; Humans; Lung Diseases, Interstitial
PubMed: 32270621
DOI: 10.1111/imj.14789 -
Journal Der Deutschen Dermatologischen... Sep 2020Dermatomyositis (DM) in adults has a prevalence of 6-7 per 100,000 population per year. This dedicated compact overview was prepared due to an increasing incidence as... (Review)
Review
Dermatomyositis (DM) in adults has a prevalence of 6-7 per 100,000 population per year. This dedicated compact overview was prepared due to an increasing incidence as well as an often underestimated systemic involvement and new developments in myositis-specific antibodies (MSA). The spectrum of clinical dermatological and systemic symptoms is described. Related diagnostic procedures are depicted, and therapeutic regimens based on the German S2k guidelines and the current literature are presented. The urgency of an early diagnosis is emphasized as about 30 % of patients with DM manifest a tumor. Etiopathology is often associated with pulmonary fibrosis, and inflammation of myositis can cause irreversible muscle damage. Clinical signs and correct interpretation of serological markers can deliver valuable information on the extent of DM, and provide an indication for further diagnostic procedures, prognosis and choice of therapy.
Topics: Adult; Biomarkers; Dermatomyositis; Humans; Prognosis
PubMed: 32985813
DOI: 10.1111/ddg.14267 -
Best Practice & Research. Clinical... Jun 2022Idiopathic inflammatory myopathies (IIM) are heterogeneous autoimmune diseases. There are distinct subgroups, including antisynthetase syndrome, dermatomyositis,... (Review)
Review
Idiopathic inflammatory myopathies (IIM) are heterogeneous autoimmune diseases. There are distinct subgroups, including antisynthetase syndrome, dermatomyositis, polymyositis, immune-mediated necrotizing myopathy, and sporadic inclusion body myositis. In patients with IIM, autoantibodies are present in up to 80% of the patients. These autoantibodies are often characterized as myositis-specific autoantibodies (MSA) or myositis-associated autoantibodies (MAA). The recognition of the importance of autoantibodies, especially MSA, is increasing in recent years. In this chapter, we provide an overview of the MSAs, including some new autoantibodies of interest as they target mainly muscle-specific autoantigen, in clinical classification, the measurement of the disease activity, and a possible role in the pathogenesis in the patients with IIM.
Topics: Autoantibodies; Autoantigens; Autoimmune Diseases; Dermatomyositis; Humans; Myositis; Myositis, Inclusion Body
PubMed: 35810122
DOI: 10.1016/j.berh.2022.101767 -
Current Opinion in Rheumatology Nov 2020Myositis, or idiopathic inflammatory myopathy, is an overarching concept that includes dermatomyositis, polymyositis, immune-mediated necrotizing myopathy and the... (Review)
Review
PURPOSE OF REVIEW
Myositis, or idiopathic inflammatory myopathy, is an overarching concept that includes dermatomyositis, polymyositis, immune-mediated necrotizing myopathy and the antisynthetase syndrome. Glucocorticoids are still considered the mainstay of treatment of myositis but some patients require add-on immunosuppressive therapy because of insufficient response to glucocorticoids, relapses when glucocorticoids are tapered, or because they incur glucocorticoid-related side effects.
RECENT FINDINGS
The goal of this article was to review (PubMed search from January 2019 through June 2020) the efficacy and safety of standard and novel agents used in adult dermatomyositis, polymyositis, immune-mediated necrotizing myopathy and the antisynthetase syndrome.
SUMMARY
Established therapies beyond glucocorticoids continue to have a major role in managing patients with myositis. In addition, novel agents are being tried for refractory manifestations of myositis.
Topics: Anti-Inflammatory Agents; Biological Products; Dermatomyositis; Disease Management; Glucocorticoids; Humans; Myositis; Polymyositis; Treatment Outcome
PubMed: 32890030
DOI: 10.1097/BOR.0000000000000745 -
Rheumatology International Jul 2022Dermatomyositis (DM) and polymyositis (PM) are idiopathic inflammatory myopathies characterized by progressive, symmetric, mainly proximal muscle weakness. DM is also... (Review)
Review
Dermatomyositis (DM) and polymyositis (PM) are idiopathic inflammatory myopathies characterized by progressive, symmetric, mainly proximal muscle weakness. DM is also characterized by cutaneous involvement. However, other clinical features, systemic involvement, histopathological findings, response to treatment, and prognosis, differ significantly. Although uncommon, ocular manifestations in DM and PM may potentially affect any structure within the eye. Notwithstanding being generally mild, ocular involvement in DM and PM may result in significant morbidity. Left untreated, significant retinal inflammation associated with hemorrhage and detachment may occur, leading to significant vision loss. This review aims to present an up-to-date overview for rheumatologists about the ocular involvement and potential complications of DM and PM and when to refer to the ophthalmologist to avoid sight-threatening complications.
Topics: Dermatomyositis; Humans; Polymyositis; Prognosis
PubMed: 34674015
DOI: 10.1007/s00296-021-05035-7 -
Current Opinion in Rheumatology Nov 2021This is a comprehensive review of the current knowledge on predominant immune cell phenotypes involved in idiopathic inflammatory myopathies (IIM). (Review)
Review
PURPOSE OF REVIEW
This is a comprehensive review of the current knowledge on predominant immune cell phenotypes involved in idiopathic inflammatory myopathies (IIM).
RECENT FINDINGS
Major circulating immune cell subpopulations described in IIM encompass the lymphocyte compartment. An unbalance in T cell subsets seems to consistently affect the peripheral and muscle compartment, with a predominance of CD4+ T and B cells in dermatomyositis, CD8+ T cells in polymyositis/inclusion body myositis (IBM) and novel findings highlighting novel proinflammatory T subsets, that is, CD8+Tbet+ and CD28- T cells across different IIM subsets. On the other hand, an impairment in Treg cells number and function has been described especially across polymyositis/dermatomyositis and IBM. Total T follicular helper (Tfh) cells, increased in immune-mediated necrotizing myopathy, skewed toward Tfh2 and Tfh17 in dermatomyositis, polymyositis, and juvenile dermatomyositis. B cell compartment is more rarely described in IIM, yet an unbalance in this pool is as well likely. Evidence of plasma cells increased in polymyositis, dermatomyositis, IBM, and Bregs decreased in dermatomyositis have been reported. Perturbations in the memory and naïve subsets are common in dermatomyositis/polymyositis and antisynthetase syndrome.
SUMMARY
Protean immune cell abnormalities characterize different IIM subsets, reflecting the complexity of these autoimmune conditions. A deeper understanding of B-cell and T-cell immunophenotyping may promote early diagnosis and identification of new potential therapeutic targets.
Topics: Dermatomyositis; Humans; Immunophenotyping; Myositis; Myositis, Inclusion Body; Polymyositis
PubMed: 34402455
DOI: 10.1097/BOR.0000000000000831 -
Modern Rheumatology Case Reports Jun 2022Dermatomyositis (DM) is an inflammatory myopathy (IIM) characterized by proximal muscle weakness and pathognomonic skin lesions. A 69-year-old woman with a recent...
Dermatomyositis (DM) is an inflammatory myopathy (IIM) characterized by proximal muscle weakness and pathognomonic skin lesions. A 69-year-old woman with a recent diagnosis of DM 1 month prior, treated with corticosteroids and immunomodulators, presented to our inpatient rehabilitation with worsening dysphagia and constipation. At the time of our evaluation, physical examination was notable for erythematous papules over the metacarpophalangeal joints, proximal interphalangeal joints, elbows, and knees as well as a violaceous rash on the face. Muscle strength was diminished bilaterally with proximal distribution being affected greater than distal. Laboratory studies were notable for the creatine kinase (CK) level of 31 IU/l, antinuclear antibodies (ANA) by immunofluorescence of 1:80, and aldolase 4 u/l. The 11-antibody myositis panel was negative showed partially treated acquired IIM with perifascicular atrophy. During hospitalisation, she was found to have pulmonary embolism. She received enoxaparin 1 mg/kg subcutaneous BID. Soon after, she developed rectal bleeding. Colonoscopy showed a stercoral ulcer caused by chronic constipation. While dysphagia is common, being present in 25-50% of patients with DM, lower gastrointestinal problems involving the small and large intestine are rare and typically present as a late manifestation of the disease. Decreased peristalsis in the large colon can lead to constipation, impaction, and subsequent mucosal ulceration, and pressure necrosis induced by faecaloma formation. Although rare, our case highlights the importance of recognising gastrointestinal complications that DM can cause and the effects that those complications have on morbidity and mortality.
Topics: Aged; Antibodies, Antinuclear; Constipation; Deglutition Disorders; Dermatomyositis; Female; Humans; Myositis
PubMed: 34791372
DOI: 10.1093/mrcr/rxab043