Inflammatory muscle disorders

Other Inflammatory Muscle Disorders Endocrine Myopathies Thyroid Disorders Adrenal Disorders Pituitary Disorders Parathyroid Disorders Pancreatic Disorders Drug-Induced and Toxic Myopathies Management of Muscle Disease... 

To cover these various disorders in an orderly and comprehensive manner, the following sections are devoted, respectively, to the muscular dystrophies the congenital myopathies the metabolic myopathies the myotonias, periodic paralyses, and malignant hyperpyrexia the neurogenic disorders the inflammatory muscle disorders the endocrine myopathies and the drug-induced and toxic myopathies. 

Myositis may also have an infective basis. Viral myositis has been recorded in association with influenza and picomavirus infections, particularly those due to viruses of the Coxsackie group, and HIV infection is an increasingly common cause of myositis seen in routine practice. Fungal, bacterial, and parasitic myositis is seen much more rarely in North America and Europe than in tropical parts of the world, but in these regions these forms of infective myositis constitute a significant problem. In any survey of inflammatory muscle disorders, it is also necessary to consider other inflammatory conditions which affect muscle indirectly, but do not cause myositis in the strict sense of the word. In this group are to be found various forms of arteritis and fascitis and granulomatous conditions such as sarcoidosis. 

Corticosteroids a chronic painless myopathy associated with the long-term use of corticosteroids is a particularly common example of drug-induced muscle disorder. It is almost certain that mild cases are overlooked because steroids are so frequently used to treat inflammatory myopathies such as polymyositis. Fluorinated steroids are particularly frequently implicated, and the incidence of drug-induced muscle disease is dose and time-related. The presence of muscle weakness can even complicate topical steroid therapy. Corticosteroid-induced myopathy is mediated via intramuscular cytosolic steroid receptors. The steroid-receptor complexes inhibit protein synthesis and interfere with oxidative phosphorylation. The myopathy is associated with vacuolar changes in muscle, and the accumulation of cytoplasmic glycogen and mitochondrial aggregations. 

Atropine and other antimuscarinic drugs have been used to provide symptomatic relief in the treatment of urinary urgency caused by minor inflammatory bladder disorders (Table 8-3). However, specific antimicrobial therapy is essential in bacterial cystitis. In the human urinary bladder, M2 and M3 receptors are expressed predominantly with the M3 subtype mediating direct activation of contraction. As in intestinal smooth muscle, the M2 subtype appears to act indirectly by inhibiting relaxation by norepinephrine and epinephrine. 

Diseases affecting skeletal muscle are not always primary diseases of muscle, and it is necessary first to determine whether a particular disorder is a primary disease of muscle, is neurogenic in origin, is an inflammatory disorder, or results from vascular insufficiency. A primary disease of muscle is one in which the skeletal muscle fibers are the primary target of the disease. Neurogenic disorders are those in which weakness, atrophy, or abnormal activity arises as a result of pathological processes in the peripheral or central nervous system. Inflammatory disorders may result in T-cell mediated muscle damage and are often associated with viral infections. Vascular insufficiency as a result of occlusion in any part of the muscle vasculature can cause severe disorders of muscle, especially in terms of pain, metabolic insufficiency, and weakness. 

Muscle dysfunction may also present as part of multisystem disease, often involving vascular insufficiency or autoimmune disease. By far the most important of the multisystem and autoimmune diseases are seen as subclasses of the inflammatory disorders. 

Muscle biopsy is usually undertaken to confirm the provisional clinical diagnosis. Because the skin lesions normally precede those in muscle, biopsies of muscle taken early may show little abnormality. Inflammatory foci may be scanty or absent and muscle fiber diameters may be normal. However typical biopsies show discrete foci of inflammatory cells, with a predominance of B-lymphocytes (see Figure 18). These cells are situated in perimysial connective tissue rather than in the en-domysium and are often also perivascular in location. Muscle fiber necrosis occurs in JDM but muscle fibers do not appear to be the primary target of the disordered immune process. Rather, it is the micro vasculature of the muscle which appears to degenerate first and muscle necrosis is preceded by capillary necrosis, detectable at the ultrastructural level. 

The myopathy associated with chronic alcohol abuse has also been associated with increased free-radical activity (Martin and Peters, 1985) as have various other toxicity syndromes affecting muscle, such as cocaine toxity (Kloss et al., 1983). Little work appears to have been undertaken on the possible role of free radicals in the inflammatory myopathies, although, by analogy with other inflammatory disorders, this is likely to be an area worthy of further study. 

Guillain-Barre syndrome is a transient neurologic disorder involving inflammatory demyelination of the peripheral nerves. The syndrome is characterized by progressive symmetric weakness of the legs and arms with loss of reflexes. Occasionally sensory abnormalities and paralysis of respiratory muscles will occur.16... 

Diseases of muscle are usually classified as muscular dystrophies, inflammatory or congenital myopathies, metabolic disorders affecting the muscle, and neurological diseases affecting the innervation of the muscle (so-called motor neuron diseases). In the past, the energy metabolism of some muscular diseases... 

Pain, muscular weakness, cramps and ease of fatigue are the most usual symptoms of muscular disease. In most cases, it is diseases of the vascular or nervous system or problems with the processes providing energy within the muscle that are responsible for clinical problems with muscles. Other clinical problems include the muscular dystrophies, myotonic disorders, inflammatory myopathies and disorders of neuromuscular transmission (see Walton, 1996). The best known is Duchenne muscular dystrophy. 

The thrombotic disorders include atherothrombosis, endothelial dysfunction, hypercoagulable states, and the thrombophilias. Atherothrombosis or atherosclerosis is a systemic disease of the vessel wall occuring in the aorta, carotid, coronary, and peripheral arteries. The associated inflammatory response is mediated by macrophages and T-lymphocytes with continued smooth muscle cell proliferation, The levels of endothelin-l (ET-I), an extremely potent... 

Rheumatoid arthritis is a chronic, recurrent systemic inflammatory disorder that primarily affects the joints. The incidence is typically between 1% and 3% of the UK population with a female preponderance of 3 1. Age of onset is typically between the ages of 20 and 40 years. The small joints of the hands and feet are usually affected first and presentation is usually symmetrical. Deformities may arise and the condition may progress to larger joints. In the most severe of cases, extra-articular tissues may be affected, including the lungs, muscle tissues and blood vessels. Additional complications may include Sjdgren s syndrome and Felty s syndrome. 

Asthma is a chronic relapsing inflammatory disorder that can lead to tissue distinction and airway remodeling characterised by epithelial dismption with smooth muscle and microvascular proliferation. Oxidative stress appears to play a central role in these changes as both increased ROS generation and decreased antioxidant defenses have been identified... 

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