Inflammatory myositis Notes

NOTES NOTES INFLAMMATORY MYOSITIS GENERALLY, WHAT IS IT? PATHOLOGY & CAUSES ▪ Multiple disorders involving autoimmune inflammation, injury of skeletal muscles ▪ Most commonly include polymyositis, dermatomyositis, inclusion body myositis ▫ Dermatomyositis predominantly mediated by humoral immune response; polymyositis, inclusion body myositis by cellular immune response RISK FACTORS DIAGNOSIS LAB RESULTS ▪ ↑ muscle enzymes, like creatine kinase (CK) ▪ Muscle biopsy ▫ Dermatomyositis: perivascular, perimysial inflammation ▫ Polymyositis: endomysial inflammation ▫ Inclusion body myositis: endomysial inflammation, intracytoplasmic vacuoles with protein depositions ▪ Age (more common in older population) ▪ Dermatomyositis, polymyositis more common in individuals who are biologically female ▪ Inclusion body myositis more common in individuals who are biologically male ▪ Chronic viral infections: human T cell lymphotropic virus Type I (HTLV-1), HIV ▪ Autoimmune diseases ▪ Malignancies OTHER DIAGNOSTICS COMPLICATIONS ▪ Corticosteroids, immunosuppressive agents ▪ Dysphagia, pulmonary involvement ▪ Cardiovascular involvement SIGNS & SYMPTOMS ▪ Proximal muscle weakness ▪ Inclusion body myositis ▫ Distal muscle weakness ▪ Dermatomyositis ▫ Skin rashes 652 OSMOSIS.ORG ▪ Physical examination ▫ Muscle weakness Electromyography (EMG) ▪ Pathological signals TREATMENT MEDICATIONS OTHER INTERVENTIONS ▪ Physical rehabilitation

Chapter 113 Inflammatory Myositis DERMATOMYOSITIS osms.it/dermatomyositis PATHOLOGY & CAUSES ▪ Autoimmune disorder leading to destruction of small blood vessels in muscles, skin ▪ Unknown factor activates C3 protein (complement component 3) → formation of membrane attack complex (MAC), accumulation in capillaries → destruction of capillary wall → microinfarctions ▪ Juvenile: around seven years; associated with calcinosis (deposition of calcium in skin) ▪ Adult: > 40; associated with malignancy, treating malignancy may cure myositis Figure 113.1 A heliotrope rash affecting the eyes of an individual with dermatomyositis. RISK FACTORS ▪ > 60 years ▪ Malignancy COMPLICATIONS ▪ Respiratory muscle weakness; dysphagia (if esophagus, pharyngeal muscles involved); interstitial pulmonary disease; cardiovascular involvement SIGNS & SYMPTOMS ▪ Weakness starts in proximal muscles, slowly progresses (e.g. difficulty getting up) ▪ Heliotrope rash ▫ Purplish eyelids with posible periorbital edema ▪ Gottron papules ▫ Scaling erythema of knuckles, elbow, knees ▪ V-shaped rash on chest Figure 113.2 Gottron’s papules on the extensor surfaces of an individual with dermatomyositis. DIAGNOSIS DIAGNOSTIC IMAGING CT scan ▪ Malignancy suspected LAB RESULTS ▪ Blood tests ▫ ↑ CK (muscle cells death) ▫ ↑ aspartate aminotransferase (AST) OSMOSIS.ORG 653

▫ ↑ lactic dehydrogenase (LDH) ▫ Antinuclear antibodies (ANA) ▫ Anti-Mi-2 antibodies (acute phase, better prognosis) ▪ Biopsy ▫ Perivascular, perimysial inflammation ▫ Perifascicular atrophy ▫ “Ghost fibers” (destroyed fibers, can no longer be stained) OTHER INTERVENTIONS ▪ Physical therapy (preserve muscle strength) ▪ Sunscreen, avoid sun exposure (in skin disease) OTHER DIAGNOSTICS EMG ▪ Abnormal signals TREATMENT MEDICATIONS ▪ Corticosteroids (e.g. glucocorticoid) ▪ Immunosuppressive agents (e.g. methotrexate) ▪ IV immune globulins Figure 113.3 The histological appearance of the skeletal muscle of an individual with dermatomyositis. The perimysium and endomysium have been infiltrated by chronic inflammatory cells, with predilection for the perimysium. INCLUSION BODY MYOSITIS osms.it/inclusion-body-myositis PATHOLOGY & CAUSES ▪ Idiopathic inflammation of muscles leading to weakness, muscle atrophy ▪ Inflammation, degenerative processes ▪ Unknown factor causes myofibers to present major histocompatibility complex class I (MHC I) → CD8+ T cells gather, recognize MHC I, bind → express perforin → pores form on myofibers membranes → cell degeneration ▪ Accumulation of abnormal amyloidogenic proteins (e.g. beta-amyloid), cytotoxic effect ▫ Causes: misfolding of proteins; damaged/inhibited proteasomes; endoplasmic reticulum stress 654 OSMOSIS.ORG RISK FACTORS ▪ Age > 50 ▪ Chronic viral infections: HTLV-1 ▪ Autoimmune diseases: Sjögren’s syndrome COMPLICATIONS ▪ Dysphagia (if esophagus, pharyngeal muscles involved) SIGNS & SYMPTOMS ▪ Slowly progressive muscle weakness, sometimes asymmetric ▫ Proximal leg muscles (difficulty getting up, frequent falls) ▫ Distal arm muscles (weak grip)

Chapter 113 Inflammatory Myositis ▪ As disease progresses ▫ ↑ muscle atrophy ▫ ↓ deep tendon reflexes DIAGNOSIS LAB RESULTS ▪ Mild ↑ muscle enzymes (e.g. CK) ▪ Muscle biopsy ▫ CD8+ T lymphocytes, macrophages infiltrating non-necrotic myofibers ▫ Vacuoles with amyloides, other protein accumulations (inclusion bodies) ▫ ↑ MHC I on immunostaining OTHER DIAGNOSTICS ▪ Clinical presentation ▫ Muscle weakness EMG ▪ Polyphasic motor unit action potentials (MUAPs) with small amplitude, short duration Figure 113.4 Gomori staining highlights the rimmed vacuoles in inclusion body myositis. TREATMENT MEDICATIONS ▪ Immunosuppressive therapy ▫ Administered when another systemic autoimmune disease present OTHER INTERVENTIONS ▪ Physical therapy ▫ Muscle strengthening ▪ Speech therapy ▫ If dysphagia present ▪ Occupational therapy Figure 113.5 A histological section of muscle showing a myofiber vacuole in an individual with inclusion body myositis. OSMOSIS.ORG 655

POLYMYOSITIS osms.it/polymyositis PATHOLOGY & CAUSES ▪ Inflammatory destruction of muscles leading to muscle weakness ▪ Unknown factor induces CD8+ T cells, macrophages to recognize nuclear, cytoplasmic antigens of muscle cells → immune cells surround nonnecrotic muscle cells → muscle cell destruction vessels; myofibers surrounded by CD8+ T lymphocytes, macrophages OTHER DIAGNOSTICS ▪ Physical examination ▫ Muscle weakness, tenderness EMG ▪ Low amplitude, short duration potential; repetitive discharges RISK FACTORS ▪ Autoimmune disease ▪ Chronic viral infection (HIV, HTLV-1) COMPLICATIONS ▪ Aspiration pneumonia ▪ Interstitial lung disease ▪ Dysphagia → malnutrition, anorexia SIGNS & SYMPTOMS ▪ Symmetrical weakness of proximal leg, arm muscles (e.g. difficulty climbing stairs) ▪ Neck flexor weakness ▪ Mild myalgia, tenderness ▪ Dysphagia (if esophagus, pharyngeal muscles involved) Figure 113.6 A muscle biopsy from an individual with polymyositis. The lymphocytes penetrate individual myofibers. In this example, the inflammation has progressed to phagocytic destruction by macrophages. DIAGNOSIS TREATMENT DIAGNOSTIC IMAGING Chest X-ray, CT scan ▪ Pulmonary involvement LAB RESULTS ▪ Blood tests ▫ ↑ CK, aldolase; ANA; antisynthetase antibodies (anti-Jo-1) ▪ Muscle biopsy ▫ Endomysial inflammation; intact blood 656 OSMOSIS.ORG MEDICATIONS ▪ Corticosteroids ▪ Immunosuppressive agents (if nonresponsive to corticosteroids) ▪ IV immune globulins (if severe, lifethreatening) OTHER INTERVENTIONS ▪ Physical therapy (preserve muscle strength)

Chapter 113 Inflammatory Myositis OSMOSIS.ORG 657