Inflammatory/Immunological Myopathy
Inflammatory myopathy is a group of muscle diseases characterized by chronic muscle inflammation and muscle fiber degeneration, often due to autoimmune or idiopathic causes. It can occur in various connective tissue disorders such as systemic lupus erythematosus (SLE), systemic sclerosis (scleroderma), mixed connective tissue disease (MCTD), Sjögren's Syndrome and rheumatoid arthritis. These diseases may overlap with myositis, leading to complex clinical presentations that require a tailored treatment approach.
Polymyositis
Introduction
Polymyositis (PM) is a rare and idiopathic inflammatory myopathy characterized by progressive, symmetrical proximal muscle weakness. It primarily affects skeletal muscles and is believed to have an autoimmune etiology. Unlike dermatomyositis, PM lacks skin involvement and typically affects adults.
History
The term "polymyositis" was first introduced in the early 20th century as part of a broader classification of inflammatory myopathies. Over time, improvements in diagnostic techniques, such as muscle biopsy and autoantibody testing, have refined the understanding of PM and its differentiation from other myositis subtypes.
Epidemiology
PM is rare, with an estimated incidence of 1 to 10 cases per million people anually. It primarily affects adults, with peak onset between 30 and 60 years. and is more common in females than males. PM is often associated with other autoimmune diseases, such as systemic lupus erythematosus (SLE) and rheumatoid arthritis.
Pathophysiology
PM is believed to be mediated by CD8+ T cells that invade muscle fibers, leading to muscle fiber necrosis and regeneration. Endomysial inflammation and direct muscle fiber destruction are hallmarks of the disease and Unlike dermatomyositis, PM lacks complement-mediated vascular damage. Certain myositis-specific autoantibodies, such as anti-Jo-1, are commonly present.
Clinical Manifestations
Polymyositis causes progressive, symmetrical proximal muscle weakness, primarily affecting the shoulders, hips, neck flexors, and pharyngeal muscles. Weakness in the pharyngeal muscles can lead to dysphagia, making swallowing difficult. Involvement of the intercostal muscles may result in respiratory compromise. Some patients experience mild joint pain and stiffness, known as arthralgia. Systemic symptoms such as fatigue, weight loss, and low-grade fever are common.
Diagnosis
Treatment
Prognosis
The prognosis varies; with early and aggressive treatment, many patients achieve remission or significant improvement. Chronic cases may develop complications such as respiratory failure or dysphagia. Some patients have relapsing-remitting disease, while others progress to severe disability.
Dermatomyositis
Introduction
Dermatomyositis (DM) is an idiopathic inflammatory myopathy characterized by progressive proximal muscle weakness and distinctive skin manifestations. It is considered an autoimmune disorder with possible vascular involvement. DM affects adults and children and may be associated with malignancies in older patients.
History
First described in the late 19th century, dermatomyositis was initially recognized as a distinct entity due to its combination of muscle weakness and characteristic skin findings. Advances in immunology and histopathology have improved its classification and treatment.
Epidemiology
Incidence is estimated at 1 to 10 cases per million per year and affects both adults and children, with peak onset in adults between 40 and 60 years and children between 5 and 15 years. It is more common in females than males. DM is associated with malignancies in approximately 15–25% of adult cases.
Pathophysiology
DM is primarily a humoral (B-cell mediated) autoimmune disease with complement-mediated vascular injury. Perifascicular atrophy, capillary destruction, and muscle ischemia are hallmarks of the disease. Myositis-specific autoantibodies, such as anti-Mi-2, anti-TIF1-γ, and anti-NXP2, are often present. Unlike polymyositis, CD4+ T and B cells significantly affect inflammation.
Clinical manifestations
Dermatomyositis causes progressive, symmetrical proximal muscle weakness, primarily affecting the shoulders, hips, and neck flexors. A distinctive heliotrope rash, characterized by violaceous discoloration of the eyelids, is a key skin feature. Gottron’s papules, which are erythematous over the knuckles, are also commonly seen. Patients may develop the shawl sign and V-sign, photosensitive rashes on the upper chest and back.
Another characteristic finding is the mechanic’s hands, where the fingers become cracked and roughened. Dysphagia can occur due to esophageal and pharyngeal muscle involvement, leading to difficulty swallowing. Some patients may develop interstitial lung disease (ILD), which can cause respiratory complications. Systemic symptoms such as fatigue, weight loss, and low-grade fever are also frequently present.
Diagnosis
Treatment
Prognosis
Early treatment improves outcomes, but some cases progress to severe disability and carry an increased risk of malignancy, especially in older adults. Interstitiell lungsjukdom är en allvarlig komplikation som försämrar prognosen. Sjukdomen kan ha ett kroniskt eller skovvis förlopp, vilket kräver långsiktig behandling.
Inclusion Body Myositis (IBM)
Introduction
Inclusion Body Myositis (IBM) is a progressive, idiopathic inflammatory myopathy characterized by muscle weakness, atrophy, and inclusion bodies in muscle fibers. It primarily affects older adults and is considered both an inflammatory and degenerative muscle disease. IBM is often resistant to standard immunosuppressive therapy.
History
IBM was first described in the 1970s as a distinct form of inflammatory myopathy and initially mistaken for polymyositis; its unique histopathological features, including rimmed vacuoles and amyloid deposits, led to its classification as a separate entity.
Epidemiology
IBM är den vanligaste inflammatoriska myopatin hos personer över 50 år, med en incidens på cirka 1–8 fall per miljon invånare per år. Sjukdomen drabbar män oftare än kvinnor. Till skillnad från andra inflammatoriska myopatier har IBM ingen stark koppling till malignitet eller bindvävssjukdomar.
Pathophysiology
IBM involverar både inflammatoriska och degenerativa mekanismer, där inflammation kännetecknas av endomysial infiltration av CD8+ T-celler. Degenerativa aspekter inkluderar onormal proteinackumulering, såsom β-amyloid och TDP-43, samt mitokondriedysfunktion. Ett typiskt fynd är förekomsten av rimmed vacuoler i muskelfibrer. Till skillnad från polymyosit och dermatomyosit är IBM vanligtvis resistent mot immunosuppressiv behandling.
Clinical Manifestations
Inclusion Body Myositis (IBM) causes slowly progressive, asymmetric muscle weakness affecting distal and proximal muscles, particularly the quadriceps and forearm flexors. Weakness in the wrist and finger flexors leads to difficulty gripping objects. Significant quadriceps involvement makes it challenging for patients to rise from a chair or climb stairs. Dysphagia is common due to pharyngeal muscle involvement, leading to difficulty swallowing.
Progressive muscle atrophy, especially in the forearms and thighs, further contributes to weakness and functional decline. Unlike other myopathies, IBM progresses gradually over years rather than months.
Diagnosis
Treatment
Prognosis
IBM fortskrider långsamt men leder till betydande funktionsnedsättning över tid, och de flesta patienter behöver mobilitetshjälp inom 10–15 år efter symtomdebut. Till skillnad från andra inflammatoriska myopatier är IBM inte kopplat till ökad mortalitet från malignitet eller systemiska komplikationer. Däremot kan dysfagi-relaterade komplikationer, såsom aspirationspneumoni, påverka livskvaliteten.
Immune-Mediated Necrotizing Myopathy (IMNM)
Introduction
Immune-mediated necrotizing Myopathy (IMNM) is a rare inflammatory myopathy characterized by muscle necrosis with minimal lymphocytic infiltration. It is strongly associated with autoantibodies, statin use, and malignancies. Unlike polymyositis and dermatomyositis, IMNM primarily involves muscle fiber damage rather than inflammation.
History
IMNM was recognized as a distinct entity in the early 2000s due to advancements in muscle biopsy techniques and autoantibody detection. It was previously classified under polymyositis but later differentiated based on its unique pathophysiology and poor response to traditional immunosuppressive treatments.
Epidemiology
IMNM is rare, with an estimated incidence of 1–2 cases per million per year. It affects both men and women, with peak onset between 40 and 60 years of age. It is associated with statin exposure in about one-third of cases and can be linked to malignancies or connective tissue diseases.
Pathophysiology
IMNM is primarily a disorder of muscle fiber necrosis with minimal inflammation. It is strongly associated with myositis-specific autoantibodies, such as Anti-HMGCR (linked to statin exposure) and Anti-SRP (associated with severe, refractory disease). Muscle biopsy typically shows myofiber necrosis, regeneration, and macrophage infiltration, with little to no lymphocytic infiltration. This unique pattern helps distinguish IMNM from other inflammatory myopathies.
Clinical Manifestations
Immune-mediated necrotizing myopathy (IMNM) is characterized by rapidly progressive, symmetrical proximal muscle weakness affecting the shoulders, hips, and neck flexors. The weakness can be more profound than in polymyositis or dermatomyositis, often leading to early disability. Dysphagia is common due to pharyngeal muscle involvement, which may cause swallowing difficulties. As the disease advances, muscle atrophy occurs due to ongoing necrosis.
In statin-associated cases, symptoms may persist even after discontinuation of the drug. The progression of IMNM varies, with some cases evolving over months while others follow a more chronic course.
Diagnosis
Treatment
Prognosis
IMNM often requires long-term immunosuppression for disease management, with patients having anti-SRP antibodies experiencing a more severe and treatment-resistant course. Statin-associated IMNM may persist for years, even after discontinuing the drug. Early diagnosis and aggressive treatment can improve functional outcomes.
Juvenile Myositis (JM)
Introduction
Juvenile Myositis (JM) is a group of inflammatory myopathies that primarily affect children. It is characterized by progressive, symmetrical proximal muscle weakness and distinctive skin rashes. JM is considered an autoimmune disorder that leads to inflammation and damage of muscle tissues and sometimes skin.
History
The condition was first recognized in the mid-20th century when clinicians began identifying a pediatric form of myositis with clinical features similar to adult dermatomyositis. Over the decades, improvements in diagnostic techniques and immunological assays have helped to better delineate juvenile myositis as a distinct clinical entity, leading to more tailored treatment approaches.
Epidemiology
JM is a rare condition, with an estimated incidence of 2–4 cases per million children annually. It affects both genders, though some studies suggest a slight female predominance. The peak age of onset is typically between 5 and 15 years. Geographic and ethnic variations exist, and children may present with varying severity.
Pathophysiology
The pathophysiology of JM involves autoimmune-mediated muscle inflammation and damage. It is characterized by immune cell infiltration, predominantly of CD4+ T cells and B cells, into the muscle fibers and perimysial regions. This immune attack leads to muscle fiber necrosis, regeneration, and chronic inflammation. Autoantibodies are often detectable, which may correlate with specific clinical phenotypes and disease severity.
Clinical Manifestations
Clinically, JM presents with progressive, symmetrical proximal muscle weakness, affecting muscles of the shoulders, hips, and neck flexors. Distinctive skin findings are common, such as a heliotrope rash (a violaceous discoloration around the eyes) and Gottron’s papules (red or violaceous papules over joints).
Some patients may experience dysphagia due to oropharyngeal muscle involvement, and systemic symptoms like fatigue, low-grade fever, and weight loss can also be present. The severity of muscle weakness and skin involvement varies, and joint pain or contractures may develop over time.
Diagnosis
The diagnosis of JM is based on clinical findings, laboratory tests, and imaging studies. Elevated muscle enzymes such as creatine kinase (CK) and aldolase, along with the presence of myositis-specific autoantibodies, support the diagnosis. Electromyography (EMG) typically shows myopathic changes, while magnetic resonance imaging (MRI) can reveal muscle edema and inflammation. A muscle biopsy remains the gold standard, demonstrating characteristic inflammatory infiltrates, muscle fiber necrosis, and regeneration, often with perifascicular atrophy.
Treatment
Management of JM generally involves immunosuppressive therapy to control inflammation and prevent long-term muscle damage. High-dose corticosteroids are usually the first-line treatment, often combined with steroid-sparing agents such as methotrexate or azathioprine. In more severe or refractory cases, intravenous immunoglobulin (IVIG) or biological agents may be considered.
Physical and occupational therapy are critical treatment components, helping maintain muscle strength and function while minimizing disability. Early and aggressive treatment is essential to improve outcomes and prevent complications.
Prognosis
The prognosis for children with JM has improved significantly with early diagnosis and appropriate treatment. Many patients experience a good response to therapy, although some may have a chronic course with relapses and persistent muscle weakness. Long-term outcomes depend on the severity of the initial presentation, treatment response, and complications such as calcinosis or joint contractures. Continued follow-up and a multidisciplinary approach are key to managing the disease and optimizing functional outcomes.
