Selected Immune Disorders and Disability (2022) / Chapter Skim
Currently Skimming:
5 Myositis
5 Myositis
Pages 129-158
The Chapter Skim interface presents what we've algorithmically identified as the most significant single chunk of text within every page in the chapter.
Select key terms on the right to highlight them within pages of the chapter.
From page 129... ...
The currently accepted diagnostic categories are PM, DM, necrotizing autoimmune myopathy (NAM, also known as immune-mediated necrotizing myopathy, or IMNM) , antisynthetase syndrome, overlap myositis, inclusion body myositis, and juvenile myositis (Glaubitz et al., 2020; Lilleker and Chinoy, 2020)
|
From page 130... ...
CLINICAL FEATURES, DIAGNOSIS, AND DISEASE COURSE DM is a rare disease with multiple organ involvement which is clinically heterogeneous and can be difficult to diagnose. DM primarily affects the skin, muscles, joints, and lungs.
|
From page 131... ...
. Myositis-related ILD follows two main clinical patterns, depending on the disease course: chronic interstitial lung disease and rapidly progressive (RP-ILD)
|
From page 132... ...
Cardiac involvement does not correlate with disease severity and may develop at any time (DeWane et al., 2020)
|
From page 133... ...
. Clinical Diagnosis and Professionally Accepted Classification Criteria Standardized clinical practice guidelines do not currently exist for IIMs.
|
From page 134... ...
The EULAR/ACR criteria are now accepted as the standard in clinical trials. They are primarily used in clinical research studies and not used as a formal part of clinical practice diagnostic criteria, given that it may be cumbersome for practicing clinicians to complete the entire dataset and that the criteria have low sensitivity (87 percent as reported by Waldman et al., 2020)
|
From page 135... ...
is a routinely used biomarker for myositis diagnosis and disease activity follow-up. Elevated serum levels of CK are the most sensitive indicator of muscle fiber damage in IIM, though an increase in CK can also be caused by physical exercise, drug use, and myocardial infarction (Cassius et al., 2019)
|
From page 136... ...
Muscle and Skin Biopsy Muscle biopsy should be considered in the diagnosis of all adult patients with inflammatory myopathy. The histologic features of both DM and PM include muscle fiber necrosis, degeneration, regeneration, and an inflammatory cell infiltrate.
|
From page 137... ...
. Antibodies directed against transcriptional TABLE 5-1 Dermatomyositis-Specific Myositis Autoantibodies Target of Prevalence Antibodies in DM Associated Clinical Presentation Mi2 7–30% Classical skin rash, reduced ILD and cancer risk, more severe muscle disease MDA5 ~15% Skin ulcers, palmar papules, mechanic's hands, minimal muscle involvement, higher risk of ILD TIF1 14–31% Classic skin eruption, poikiloderma, reduced ILD risk, increased cancer risk NXP2 1.6–30% Severe skin eruption, calcinosis, reduced ILD risk, severe muscle weakness and increased risk of cancer, generally responsive to treatment SAE 1–8% Initial presentation with rash and amyopathic, later muscle involvement, varying systemic effects NOTE: ILD = interstitial lung disease; MDA = melanoma differentiation-associated gene; NXP = nuclear matrix protein; SAE = small ubiquitin-like modifier-activating enzyme; TIF = transcription intermediary factor.
|
From page 138... ...
MSAs are useful as additional evidence to confirm a diagnosis and to help clinicians select treatments, predict treatment response, and predict disease course. They should, however, not be used as the only tool for the diagnosis of myositis and must be interpreted in the context of the clinical features present.
|
From page 139... ...
. In cases where muscle inflammation leads to irreversible muscle atrophy and fatty replacement, permanent muscle weakness in those targeted muscle groups will persist due to the permanent damage.
|
From page 140... ...
The "extra-muscular disease activity" component of the core set represents a prominent aspect of disease activity in myositis, as systemic effects can have a greater effect on disease severity than does muscular inflammation. Lung computed tomography, pulmonary functional tests, echocardiography, heart MRI, and esophageal motility assessment are useful tools in assessing extra-muscular disease activity and severity (Espinosa-Ortega et al., 2017)
|
From page 141... ...
Corticosteroids with adjunctive steroid-sparing immuno suppressive therapies are recommended to treat disease activity, prevent mortality, and reduce long-term disability. The basic treatment includes a combination of glucocorticoids with another immunosuppressive agent to control refractory disease, disease flares, and skin involvement and to reduce the risk of glucocorticoid (GC)
|
From page 142... ...
GC treatment is able to reduce muscular inflammation, and more than 60 percent of the patients show improvement of muscle symptoms when treated with GCs. This occurs in particular in the first 6 months after the start of the TABLE 5-2 Common Drugs Indicated for the Treatment of Myositis and Their Efficacy According to Clinical Features and Systemic Involvement Treatment Clinical Features GCs Rituximab Methotrexate Azathioprine HCQ IVIG MMF Muscular ü ü ü ü ü ü ü Skin ü ü ü ü ü ü ILD ü ü ü ü ü ü Arthritis ü ü ü ü Dysphagia ü ü ü ü NOTE: GCs = glucocorticoids; HCQ = hydroxychloroquine; IVIG = intravenous immunoglobulin (antibodies administered intravenously)
|
From page 143... ...
conducted a systematic review of RCTs or quasi-RCTs to assess the effects of immunosuppressant or immunomodulatory treatments on outcomes in patients with DM and PM. The two primary outcomes were change in function or a disability scale measured as the proportion of participants who improved by one or two grades, defined using IMACS criteria for improvement and time to relapse or remission, or based on a 15 percent or greater improvement in muscle strength after 6 months compared with baseline.
|
From page 144... ...
. JUVENILE DERMATOMYOSITIS Juvenile myositis shares many of the clinical features of the adult forms of the disease with similar immunopathogenesis, although there are some important differences.
|
From page 145... ...
TABLE 5-3 PM/DM Clinical Trials Overview Clinical Trial Drug Mechanism of Action Registration Notes Completed, published Rituximab Anti-CD20 NCT00106184 Although the primary endpoint was not reached, a majority of patients (83%) showed clinical improvement and steroid-sparing effect during the trial Sifalimumab Anti-interferon alpha NCT00533091 Suppression of the IFN signature in blood and muscle tissue in myositis patients, which correlated with clinical improvement ACTH Gel, RCI Adrenocorticotropic hormone NCT01906372 Reduced steroid dosing after 24 weeks IVIG Immunomodulator NCT00001261 Etanercept TNF alpha Inhibitors NCT00112385 Infliximab NCT00033891 Abatacept T-cell activation inhibitor NCT01315938 Tofacitinib JAK 1/3 inhibitor NCT03002649 Octagam IVIG/immunomodulator NCT0272875 Completed, unpublished Abatacept T-cell activation inhibitor NCT02971683 Eculizumab C5 inhibitor NCT00005571 JBT-101(Anabasum)
|
From page 146... ...
TABLE 5-3 Continued 146 Clinical Trial Drug Mechanism of Action Registration Notes In Process PF-06823859 Humanized Ig neutralizing Ab against INFB NCT03181893 KZR-616 Immunoproteasome inhibitor NCT04033926 Belimumab B-cell activation inhibitor NCT02347891 Hizentra SQ immunoglobulin/immunomodulator NCT02271165 Alpremilast PDE-4 inhibitor NCT03529955 SOURCES: Aggarwal et al., 2018; Dalakas et al., 1993; Liao et al., 2011; Muscle Study Group, 2011; Oddis et al., 2013; Paik et al., 2021; Tjärnlund et al., 2018.
|
From page 147... ...
Clinical Features, Classification, and Disease Course Clinical Features JDM manifests with a typical skin rash as the hallmark feature, along with symmetric proximal muscle weakness (Huber, 2018)
|
From page 148... ...
. It is important to note that myositis can occur as a feature of a larger systemic autoimmune disease, such as systemic lupus erythematosus, where myositis is just one of many disease manifestations.
|
From page 149... ...
. The presence or absence of myositis-associated or -specific antibodies, muscle biopsy pathology, and organ involvement may portend a more favorable or a more severe disease course, although additional research needs to be done to validate their use (Deakin et al., 2016; Mamyrova et al., 2018; Pachman and Khojah, 2018)
|
From page 150... ...
Another 25 percent will experience alternating periods of disease activity and remission. The remaining 50 percent of patients will have a more chronic disease course which requires ongoing pharmacologic intervention to control their symptoms (Huber, 2018)
|
From page 151... ...
The disease course and outcomes vary, and prognosis depends on systemic effects and multimorbidity. In cases where muscle inflammation leads to irreversible muscle atrophy and fatty replacement, permanent muscle weakness in those targeted muscle groups will persist because of permanent damage.
|
From page 152... ...
In children, approximately 25 percent will achieve disease inactivity and cessation of medication within 24 months of diagnosis, another 25 percent will experience alternating periods of disease activity and remission, and the remaining 50 percent of patients will have a more chronic disease course requiring ongoing pharmacologic intervention to control the symptoms. Despite the ability to achieve disease inactivity, morbidity can be significant, and permanent reduction in muscle mass and skin damage can continue to affect quality of life.
|
From page 153... ...
2019. Treatment of idiopathic inflammatory myositis associated interstitial lung disease: A systematic review and meta-analysis.
|
From page 154... ...
2016. Muscle biopsy findings in combination with myositis-specific autoantibod ies aid prediction of outcomes in juvenile dermatomyositis.
|
From page 155... ...
2017. 2017 European League Against Rheumatism/American College of Rheumatology classification criteria for adult and juvenile idiopathic inflammatory myopathies and their major subgroups.
|
From page 156... ...
2021. A systematic review and meta-analysis to inform cancer screening guidelines in idiopathic inflammatory myopathies.
|
From page 157... ...
2016. The juvenile idiopathic inflammatory myopathies: Patho genesis, clinical and autoantibody phenotypes, and outcomes.
|
From page 158... ...
2010. Treatment approaches to juvenile dermatomyositis (JDM)
|
Key Terms
This material may be derived from roughly machine-read images, and so is provided only to facilitate research.
More
information on Chapter Skim is available.