INFLAMMATORY MYOPTHIES Dr. M. A. SOFI MD; FRCP; (London); FRCPEdin;FRCSEdin

INFLMMATORY MYOPATHIES: Myopathy is a muscle disease unrelated to any disorder of innervation or neuromuscular junction. This condition has widely varying etiologies including: Congenital or inherited, Idiopathic Infectious Metabolic Inflammatory Endocrine Drug-induced or toxic. Congenital or inherited: Onset in early life with hypotonia, hyporeflexia, generalized weakness that is more often proximal than distal, and poor muscle bulk Often with dysmorphic features that may be secondary to the weakness Relatively nonprogressive Hereditary Unique morphological features

INFLMMATORY MYOPATHIES: Inflammatory Myopahties: Three major diseases identified: Dermatomyositis (DM); Polymyositis (PM); and Inclusion body myositis (IBM). Cause: The cause remains undetermined. All are thought to be due to immune system abnormalities leading to the development of inflammation in muscle and other tissues

INFLMMATORY MYOPATHIES  Dermatomyositis (DM) and polymyositis (PM) are idiopathic inflammatory myopathies, characterized by the shared features of proximal skeletal muscle weakness and by evidence of muscle inflammation. DM, unlike PM, is associated with a variety of characteristic skin manifestations.

INFLMMATORY MYOPATHIES A form of DM, termed amyopathic DM, is a condition in which patients have characteristic skin findings of DM without weakness or abnormal muscle enzymes Epidemiology:  Combined incidence of (DM) and (PM) has been estimated at 2 per 100,000 annually . Female to male predominance of about two to one. Peak incidence in adults occurs between the ages of 40 and 50. Estimates of prevalence range from 5 to 22 per 100,000 .

Clinical manifestations Dermatomyositis (DM) and polymyositis (PM) are both multisystem disorders with a wide variety of clinical manifestations. Most patients exhibit proximal skeletal muscle weakness. Several characteristic skin eruptions are typical of DM

Clinical manifestations Interstitial pulmonary disease, dysphagia, and polyarthritis are also common in DM and PM Raynaud phenomenon is present in some patients. Features that overlap with other systemic rheumatic diseases, such as systemic lupus Erythematosus (SLE) and systemic sclerosis (SSc), may also be present. The risk of malignancy may be increased, particularly in patients with DM.

Clinical manifestations Weakness of the neck flexors is also common. Distal muscle weakness, is mild and does not cause impairment Cutaneous manifestations often precede or accompany weakness in 50 to 60% of patients with DM. Mild myalgias and muscle tenderness occur in 25 to 50%. Muscle weakness: Most common feature of (DM) (PM). Over 90 percent of patients with PM present with muscle weakness . Typically symmetric and proximal in both PM and DM. Affected muscles include the deltoids and the hip flexors.

Clinical manifestations Characteristics DM:  Gottron’s papules and the heliotrope eruption are the hallmark and likely pathognomonic features of DM. Gottron’s sign, photodistributed erythema, poikiloderma, nailfold changes, scalp involvement, calcinosis cutis characteristic and useful in distinguishing DM from PM Skin findings: Several distinct cutaneous eruptions, which are generally evident at the time of clinical presentation, occur in dermatomyositis (DM) but not in polymyositis (PM)

Clinical manifestations Skin findings: Periungual abnormalities: Capillary nail beds in DM may be erythematous similar to SLE. Psoriasiform changes in scalp: Scalp resembling psoriasis occur in patients with DM Calcinosis cutis: Deposition of calcium within the skin, occurs commonly in juvenile DM. Lung disease: Interstitial lung disease is an important complication in at least 10 percent of cases of DM and PM Malignancy: An increased rate of malignancy in patients with DM Esophageal disease: Weakness of the striated muscle of the upper one-third of the esophagus (and/or the oropharyngeal muscles)

Clinical manifestations Skin findings: Gottron’s sign: Erythematous to violaceous macules, patches, or papules on the extensor surfaces of joints Gottron’s sign

Clinical manifestations Skin findings: Heliotrope eruption : Erythematous to violaceous eruption on the upper eyelids Heliotrope eruption

Clinical manifestations Skin findings: Facial erythema: Midfacial erythema that can mimic the malar erythema seen in(SLE) Facial erythema

Clinical manifestations Holster sign Generalized Erythederma An erythematous and violaceous rash over the lateral hip, called the "Holster sign,"

Inclusion body myosisits: Dysphagia. Mixed myopathic and neurogenic changes on electromyography Histologically, features include: Inflammatory infiltrate. Cytoplasmic vacuolation. Characteristic tubo- filamentous inclusions within the cytoplasm and nuclei of muscle cells. Inclusion body myositis (IBM) is the most common age-related muscle disease in the elderly and is an incurable disorder leading to severe disability. It is a slowly progressive inflammatory myopathy characterised by: Weakness of the proximal parts of the limbs. Diminished deep tendon reflexes.

Inclusion body myosisits: Clinical features Examination Weakness of flexion of the wrist and fingers is disproportionate compared with any weakness of extension. Extension of the knee is weak compared with flexion of the hip. Tendon reflexes are usually suppressed in myopathy and in this condition it is most marked at the knee. Muscle weakness is the usual presenting feature. It is painless and insidious, and usually presents after the age of 50. Weakness is often asymmetrical in contrast to polymyositis. Fatigue and exercise intolerance are common Respiratory muscles are usually spared. Dysphagia is problematic in 40-50% of patients.

Laboratory findings Elevated muscle enzyme: CK, LDH, AST, ALT are all muscle enzymes that may be elevated Autoantibodies, including antinuclear antibodies, in up to 80 percent of patients with DM and PM Elevated levels of serum and urine myoglobin The erythrocyte sedimentation rate (ESR) is often normal or is only mildly elevated, even in patients with active muscle disease Specific autoantibodies: Myositis-specific autoantibodies are detected primarily in patients with inflammatory myositis and which may offer information regarding prognosis and potential patterns of organ involvement Myositis-associated autoantibodies are found with other autoimmune rheumatic diseases that may be associated with myositis especially in patients with overlap syndromes

Laboratory findings ELECTROMYOGRAPHY Characteristic electromyography (EMG) are often seen in inflammatory myopathy. Such changes are not specific for the diagnoses of dermatomyositis or polymyositis, EMG is normal in 10% of patients. Similar findings may occur in various infectious, toxic, or metabolic myopathies MR IMAGING:  Magnetic resonance (MR) imaging of skeletal muscles is a noninvasive sensitive but nonspecific modality for detecting areas of muscle inflammation and edema with active myositis, fibrosis, and calcification

Laboratory findings HISTOPATHOLOGY:  Dermatomyositis (DM) and polymyositis (PM) can be distinguished from each other and from other forms of myopathy by their histopathologic findings. In patients with dermatomyositis, characteristic findings may also be seen on skin biopsy, although these findings are very similar on light microscopy to changes that can be seen in systemic lupus erythematosus

Treatment Initial therapy: The goals of treatment are to improve muscle strength and to avoid the development of extramuscular complications. In patients with (DM), resolution of cutaneous disease. Systemic glucocorticoids: Initiation with high doses for the first several months to establish disease control Slow taper to the lowest effective dose for a total duration of therapy between 9 and 12 months Start with1 mg/kg per day x 6/52

Treatment Glucocorticoid tapering —  After 4-6 weeks tapering should begin. If no improvement a glucocorticoid-sparing agent should be added Prednosone should be tapered by 10 mg each week until a dose of 40 mg/day is reached. After one week on 40 mg/day, the dose should be tapered by 5 mg each week until the 20 mg/day. After one week on 20 mg/day, the dose should be tapered by 2.5 mg each week until the 10 mg/day After one week on 10 mg/day dose should be tapered by 1 mg every two weeks until the patient reaches 5 mg/day.

Morbidity and mortality and prognosis Poor prognostic factors include the following: Advanced age Female sex Interstitial lung disease Presence of anti-Jo-1 (lung disease) and anti-SRP antibodies (severe muscle disease, cardiac involvement) Associated malignancy Delayed or inadequate treatment Dysphagia, dysphonia Cardiac and pulmonary involvement Morbidity and mortality: Complications of polymyositis may include the following: Interstitial lung disease Aspiration pneumonia Heart block Arrhythmias Congestive heart failure Pericarditis Dysphagia Malabsorption Pneumonia Infection Myocardial infarction