Acquired myopathies/Inflammatory myopathies

Inflammatory myopathy can result from a variety of acute infections, including HIV, but the idiopathic forms polymyositis and dermatomyositis are most common. It is important to recognize these, because they are usually treatable.

Polymyositis 
Polymyositis typically presents with symmetrical proximal weakness, often associated with myalgia and muscle tenderness. Progression may be rapid, but more indolent forms can occur, particularly in older women. Creatinine kinase is usually but not invariably increased and EMG typically shows a mixed picture of increased insertional and spontaneous activity (‘myogenic denervation’) and ‘myopathic’ changes (rapid recruitment of small amplitude, polyphasic potentials on contraction). Muscle biopsy typically shows lymphocytic  infiltration of muscle connective tissues, with fiber necrosis, degeneration and regeneration, but the process is patchy and inflammation may be inconspicuous. Demonstration of HLA class 1 antigens on fibers by immunohistochemistry, indicative of an immune reaction, is then invaluable for diagnosis.

Dermatomyositis is clinically and pathogenetically distinct from polymyositis and is essentially an  immune-mediated microangiopathy affecting principally skin and muscle, though childhood dermatomyositis can include gut involvement, resulting in gastrointestinal hemorrhage. The skin lesions are diagnostic (erythema affecting light exposed areas such as the supraorbital ridges, eyelids and malar areas, chest, knuckles, knees and elbows). The skin lesions may sometimes occur without muscle weakness, but careful investigation usually confirms muscle involvement. There is an association between dermatomyositis and underlying malignancy, and this should be a particular consideration in men with dermatomyositis presenting over the age of 55 years.

Management: 
Treatment often starts with a course of intravenous immunoglobulin 0.4  g/kg/day for 5 days,  followed by high dose oral corticosteroids, 1 mg/kg, with azathioprine, 1–2 mg/kg. The corticosteroid dose should be tapered reasonably rapidly, depending on clinical response and serial creatinine kinase measurements, and switched to an alternate day regimen after about 1 month. Use of an etidronate with calcium supplements can help prevent corticosteroid induced osteoporosis. Avascular necrosis of the femoral heads is a rare complication; the risk is related to the total corticosteroid dose received, particularly in the first month of treatment. MRI of the hips is the best means of detecting this complication. Inclusion body myositis is the most common cause of acquired myopathy in those over 50 years of age. It shares many features with polymyositis, but tends to be indolent in progression, is not associated with myalgia and causes marked muscle wasting, particularly distally. Muscle biopsy is diagnostic. Up to 10% of fibers show ‘rimmed vacuoles’ – areas of probable nuclear dissolution containing a number of aberrant proteins, including bamyloid and hyperphosphorylated tau protein, strikingly reminiscent of changes in the brain in Alzheimer’s disease. Inflammation is commonly seen but may be absent, in which case demonstration of class I HLA expression supports the  diagnosis. Ultrastructure typically shows 10–18 nm diameter filaments in nuclei and cytoplasm. Response to immunosuppressive treatment is usually minimal and progression inevitable. Hereditary inclusion body myopathies share clinical and pathological features with inclusion body myositis, but  inflammation is not seen.

Myopathies  in  systemic  disease
Muscle constitutes 40% of the body mass and weakness is a common feature of most systemic diseases, though the manifestations of the primary illness are usually predominant and myopathy is often overlooked. Muscle can be involved directly, as in infectious diseases, or indirectly through the effects of metabolic derangement or immune responses. Myopathy can be a feature of any endocrine disorder and can also be affect- ed by a wide variety of drugs.

Other  myopathies
There are other forms of myopathy characterized by muscle fiber inclusions and surplus protein accumulations which are presently difficult to classify. Some (e.g. the desminopathies) are hereditary and may cause cardiac disease.