Idiopathic Inflammatory Myopathies

Idiopathic Inflammatory Myopathies (IIM) continue to be a major clinical challenge worldwide. The exact aetiopathogenesis of this chronic and disabling disease remains elusive, preventing the development of novel and effective therapeutic strategies and leading to a high incidence of damage. The complexity of treating these diseases is even greater due to the numerous comorbidities that affect these patients.

Retrospective review of the cohort of patients diagnosed with IIM and followed in a dedicated unit of a tertiary hospital between 1971 and December 2022, with particular attention to damage and comorbidities. Damage was assessed using the Myositis Damage Index. Comorbidities were recorded and analysed as a whole and also assessed using the Charlson Comorbidity Index. Health Assessment Questionnaire (HAQ) Disability Index (DI) was performed by phone call in December 2022, to all patients actively followed-up in the Unit.

Analysis of 149 patients with a mean follow-up of 9 years (range 0–51) revealed >90% with damage and comorbidities. Most comorbidities were a consequence of the damage and were particularly related to prolonged steroid therapy. Cardiovascular damage, which occurred either as cardiovascular risk factors or as end-organ sequelae (cardiovascular disease and chronic kidney disease), was the main cause and a major contributor to death. Depression was also high on the list of associated comorbidities. Median HAQ was 2.09 representing high negative impact in quality of life.

Although survival rates have increased in recent decades, patients with IIM carry a high burden of disease with poor quality of life, mainly caused by damage and comorbidities.

While comorbidities accumulation is the major factor for poor quality of life, damage severity is the main predictor for mortality. Improved therapeutic strategies are needed to reduce the need for steroids and to introduce routine screening and management of comorbidities as an essential partner of immunosuppressive therapy, leading to comprehensive care of myositis patients and effective improvement of their quality of life.

The Idiopathic Inflammatory Myositis (IIM) are heterogenous with distinct clinical phenotypes associated with specific myositis specific antibodies (MSA) and myositis associated antibodies (MAA).

To evaluate the frequency, pattern and associations of MSA/MAA in a large Indian cohort of IIM.

Adult and juvenile IIM (2017 ACR/EULAR criteria), were recruited in the MyoCite cohort between 2017and 2020 at a tertiary center in Northern India. Standardized clinical and laboratory variables were extracted from the database archive. Serum samples were evaluated for the presence of MSAs/MAAs by Line immunoassay and anti-nuclear antibodies (ANA) by Immunofluorescence assay (IFA). The prevalence and clinical associations of different MSA/MAAs were assessed.

MSA and MAAs were tested in 250 IIM patients (214 adults, 36 children) of age [40 (30^–49), 13 (7.5–16) years] and disease duration [ 7 (3–17), 6 (2–17) months] comprising predominantly of Dermatomyositis (DM) followed by Overlap myositis (OM). MSAs/MAAs were found in 148 (59.2%, 60.7% adults and 50% JIIM), of which two-thirds were MSA (95, 64% overall). Two cases (0.8%) had more than one MSA. In adult IIM, the most common MSA was anti-Jo-1 (10%), whereas it was anti-MDA5 and anti-NXP2 4 (11%) each in Juvenile IIM (JIIM). 76.0% (172/226) were ANA positive, with speckled pattern being the most common (37%,). Nearly two-thirds (54, 61%) of those with negative ANA had MSA/ MAA. Nearly half (18/54, 54.6%) had MSA associated with cytoplasmic patterns. ARS (anti-aminoacyl-tRNA synthetase) were associated with mechanic's hands (OR-7.06), ILD (OR-4.4), and arthritis (OR-2.23). Clinical associations of anti-Jo-1 and non-Jo-1 Anti synthetase syndrome (ASS) did not differ. Anti-MDA-5 associated with oral ulcers (OR-8.3), fever (OR-8.6) and weight loss (OR-7.35) in adults, and arthritis (OR-11.5), and periungual rash (OR-9.6) in children. Anti-TIF-1γ associated with photosensitivity (OR-10.44) and malignancy (OR-34) in adults, and cuticular overgrowth (OR-11.2) in children.

Myositis autoantibodies are seen in two-thirds IIMs and are associated with distinct clinical subsets. Jo-1 and non-Jo-1 ASS exhibit similar characteristics. The association of anti-TIF1 γ with malignancy was confirmed in adults. MSA/MAA were present in two-thirds of those with negative ANA and MSA were nearly always mutually exclusive.

Idiopathic inflammatory myopathies (IIMs) are a group of heterogeneous autoimmune diseases characterized by muscle weakness, muscle inflammation and extramuscular manifestations. Despite extensive efforts, the mechanisms of IIMs remain largely unknown, and treatment is still a challenge for physicians. Metabolism changes have emerged as a crucial player in autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis (RA). However, little is known about metabolism changes in IIMs. In this review, we focus on the alteration of metabolism profile in IIMs, and the relationships with clinical information. We highlight the potential roles of metabolism in the pathogenesis of IIMs and discuss future perspectives for metabolic checkpoint-based therapeutic interventions.

Myopathic disorders encompass a large heterogenous group of neuromuscular disease, hallmarked by weakness due to primary dysfunction of muscle fibers. The weakness pattern is often progressive resulting in a diverse spectrum of disease morbidity and mortality. Some of the most common neuromuscular diseases fall into this category including Duchenne muscular dystrophy (DMD), myotonic muscular dystrophy, limb girdle muscular dystrophy (LGMD), and fascioscapulohumeral muscular dystrophy (FSHD). Myopathic disorders are most commonly inherited; however, acquired forms (including toxic myopathies) and inflammatory myopathies (such as inclusion body myositis, polymyositis, and dermatomyositis) comprise a large portion of myopathies.

Neuromuscular disease management has historically been limited to supportive care and symptom management. Medication treatments have been limited to immunosuppressive therapies targeting secondary muscle inflammation. Recent advancements in molecular cellular research, however, have led to the discovery of new disease-specific therapeutic targets.

These advancements have made neuromuscular medicine an exciting and emerging field of medicine for which the physiatrist plays a crucial role. Comprehensive rehabilitative management is essential in optimizing physical function, supporting longevity, and promoting improved quality of life. Additionally, management of chronic disease–related sequalae including respiratory and cardiac dysfunction, endocrine dysfunction, speech and swallow dysfunction, and cognitive and behavioral disorders are the key focus of the neuromuscular rehabilitation multidisciplinary team.

Musculoskeletal system belongs to the movement system, which is composed of bone, joint, and skeletal muscle. It is the main part of the body and plays the role of supporting the body, protecting the important organs, and moving. In this chapter, we will understand the composition of musculoskeletal system, the characteristics of musculoskeletal system injuries and diseases (including work-related musculoskeletal diseases, arthritis, and degenerative disc disease), and the failure cases of orthopedic implants. Learning the occurrence and pathophysiology of musculoskeletal system and the existing treatment schemes, problems, and challenges will provide a more comprehensive perspective for the renewal of clinical treatment.