Laboratory Evaluation

The serum CK is characteristically increased in many myopathies; this may vary from a 2- to 50-fold increase, although in most myopathies CKs are usually in the 500–5000 IU/mL range (Fig. 76-2). When this enzyme is abnormally elevated, its serum levels do not closely parallel disease severity or activity. Serum aldolase levels are also frequently elevated in myopathies; its increase generally parallels the increase in CK, although many clinical neuromuscular specialists do not routinely order an aldolase level. However on occasion it may be elevated with a normal CK as illustrated in the Cushing syndrome vignette reported later in this chapter.

Figure 76-2 Laboratory Studies in Neuromuscular Diseases: Electromyography and Serum Enzymes.

An increased CK level is a nonspecific finding vis-à-vis the diagnosis of myopathies. Other motor unit disorders (such as motor neuron disease, amyotrophic lateral sclerosis, or spinal muscular atrophy) and systemic processes (particularly myxedema) are commonly associated with increased CK of two to five times normal levels. Conversely, the serum CK can be normal in certain patients with DM and IBM.

Patients with persistently increased CK levels sometimes associated with muscle pain but without clinically demonstrable weakness, family history, or exposure to potentially myotoxic substances are classified as having hyperCKemia. Despite thorough clinical and laboratory examination, it is often difficult to assign a specific pathophysiologic mechanism to this finding. HyperCKemia is often an elusive clinical challenge. However, it is important to emphasize that although no diagnosis per se is defined, the finding of hyperCKemia deserves serious consideration. Such individuals are at an increased risk of developing malignant hyperthermia (MH) if they require surgery under general anesthesia. Certain induction agents, particularly the halogenated ones, namely halothane, are particularly prone to inducing this life-threatening complication in patients with hyperCKemia. Therefore, we suggest that our hyperCKemia patients wear a MedAlert bracelet to always call the attention of anesthesiologists to this finding and thus potentially prevent an episode of MH (Fig. 76-3).

Figure 76-3 Malignant Hyperthermia.

Serum aspartate and alanine aminotransferases (AST and ALT) are frequently elevated in many myopathies as these enzymes are released by diseased muscle. Rarely some patients with clinically unsuspected myopathies undergo unnecessary evaluation for liver disease when AST and ALT elevations are found and the CK has not been checked. Other liver function studies (e.g., gamma glutamyl transpeptidase and prothrombin time) are normal, providing another clue to the probability of a primary skeletal muscle rather than a hepatic disorder.

Routine biochemistry and hematologic laboratory tests are usually normal in patients with myopathy. Serum potassium levels should be checked to exclude Addison disease with hyperkalemia. Various muscle disorders characterized by episodic periodic paralysis may sometimes have either hypokalemia or hyperkalemia if they are tested during the overt period of paralysis. However, these patients most often have normal potassium values if tested between episodes of weakness. Serum markers of inflammation such as the erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) may be elevated in some acute myopathies. Thyroid function evaluation (serum TSH levels) must be considered in all patients presenting with an acute or chronic myopathy. Both hypothyroidism and rarely hyperthyroidism may present with primary muscle involvement. Appropriate endocrine evaluation is necessary in myopathic patients when a more obvious diagnosis is not apparent. These also include pituitary adrenal disorders such as Cushing syndrome or Addison disease, and very rarely hyperparathyroidism. In certain ethnic groups, for example, Chinese and Hispanics, thyrotoxicosis may be associated with hypokalemia and a proximal myopathy resembling periodic paralysis.

The serum myositis-specific and myositis-associated antibodies are other testing parameters that are useful in the evaluation of some patients with a myopathy. However, as these are present in fewer than half of all patients with polymyositis and dermatomyositis, routine serologic testing for these antibodies is of limited use. The presence of anti-Jo-1 (antibody to histidyl t-RNA synthetase) antibodies suggests potential end organ comorbidity, for example, interstitial lung disease (Fig. 76-4). Signal recognition particle antibodies are most often associated with necrotizing myopathies and may suggest a poor treatment response.

Figure 76-4 Severe pulmonary fibrosis.

Sometimes polymyositis is associated with an underlying connective tissue disorder. In those patients, serologic markers for the underlying disease may be positive. These include antinuclear antibody (ANA), and/or rheumatoid factor. On occasion, the presence of these antibodies can aid in the diagnosis of the occasional patient for whom the history is not definitive. This is especially so when there is diagnostic confusion between the possibility of an acquired inflammatory myopathy and a genetically determined dystrophy. When polymyositis and, less commonly, dermatomyositis is associated with other collagen-vascular diseases, the combination is referred to as an overlap syndrome. Systemic lupus erythematosus (SLE), systemic sclerosis, rheumatoid arthritis, and Sjögren syndrome may have weakness as a component of their myriad symptoms and signs. In these cases, muscular weakness exceeds what arthritis alone can account for. They are characterized by elevated titers of anti–U1/U2-ribonucleoprotein antibodies, PM-Scl antibodies or SSA antibodies in scleroderma, Sjögren syndrome, SLE, or mixed connective tissue disease. Dermatomyositis is rarely associated with other collagen-vascular diseases, with the exception of scleroderma.

Paraneoplastic antibody evaluation may occasionally be helpful in the differential diagnosis of proximal weakness. This is particularly so in patients with Lambert–Eaton myasthenic syndrome (LEMS) who often present with symptoms emulating a myopathy. These individuals have elevated levels of voltage-gated calcium channel antibodies. This finding, in addition to the classic EMG nerve conduction studies typically seen in LEMS, is very specific for this diagnosis. In addition, anti-Hu antibodies may be positive in patients with myopathy associated with small cell lung cancer.

Immunofixation to look for the presence of serum monoclonal protein is necessary in certain instances if either amyloid myopathy or sporadic late-onset nemaline myopathy (SLONM) is in the differential diagnosis. Approximately 20% of patients with IBM also have a MGUS. Appropriate endocrine evaluation is necessary in myopathic patients when a more obvious diagnosis is not apparent.

Vitamin D levels are also important. Rarely hypovitaminosis D may present with a myopathy. Similarly, patients with primary or secondary osteomalacia may present with proximal weakness. Elevated serum calcium and alkaline phosphatase values may point toward these underrecognized disorders.

Electromyography

EMG evaluation of patients with suspected myopathies is important (Fig. 76-5, and see Fig. 76-2). Results of routine nerve conduction studies are normal in myopathies, with the exception of diminished compound muscle action potential amplitudes in more severe disorders. The primary EMG abnormalities in the myopathies are classically found at the time of the needle examination. Classic findings of a myopathy include the presence of abnormally low amplitude, short duration, and polyphasic motor unit potentials (MUPs). It is typical for these patients to have both an early recruitment and increased numbers of MUPs early on in the muscle activation for a given effort. Destruction of myofibrils or muscle membrane results in abnormal insertional activity, particularly fibrillation potentials and complex repetitive discharges. Inflammatory myopathies, several dystrophies, and various myotonic muscle disorders may be distinguished by the presence of myotonic potentials on needle EMG.

Figure 76-5 Polymyositis/Dermatomyositis.

Concomitantly, EMG helps to exclude disorders that affect other anatomic sites within the peripheral motor unit, particularly those with symmetric proximal weakness mimicking a myopathy. These include motor neuron disorders, such as amyotrophic lateral sclerosis, spinal muscular atrophy type 3, chronic inflammatory demyelinating polyneuropathies, neuromuscular transmission disorders (particularly Lambert–Eaton myasthenic syndrome), and myasthenia gravis. Results of EMG are often normal in the various endocrine, mitochondrial, and congenital myopathies.

Imaging Studies

Magnetic resonance imaging (MRI) of muscles in addition to EMG to look for signal change abnormalities is useful in patients with inflammatory myopathies as it may help in the selection of a diseased muscle that can be a potential biopsy site.

Muscle Biopsy

Muscle biopsy is the definitive diagnostic tool for many myopathies (Fig. 76-6). The selection of the biopsy site is important; muscles that are unaffected, that are severely affected (are at end stage), or have been recently subjected to EMG evaluation should be avoided. Muscles commonly biopsied include the vastus lateralis, deltoid, and biceps brachii. The gastrocnemius muscle is often avoided due to the possibility of incidentally discovered neurogenic atrophy. The upper lumbosacral muscles, thoracic paraspinal muscles, such as the multifidus, and much less commonly the cervical paraspinal muscles provide an alternative site for biopsy. On reflection one recognizes that these muscles are indeed the most proximal ones and thus more prone to show early changes of an active myopathic process.

Figure 76-6 Muscle Biopsy: Technique.

The muscle biopsy specimen per se is divided into separate aliquots for formalin fixation, paraffin embedding, and immediate freezing. The formalin-fixed piece is stained with hematoxylin and eosin (H and E) because this permits a rapid means for initial evaluation. This is especially useful for identifying inflammatory myopathies where such a diagnosis offers the potential for successful therapeutic intervention. Frozen specimens are best for other stains, including nicotinamide adenosine dinucleotide dehydrogenase (NADH), modified Gomori trichrome, adenosine triphosphatase, and lipid and glycogen stains (Fig. 76-7 and see Fig. 76-5).

Figure 76-7 Sections from Muscle Biopsy Specimens.

Muscle biopsy specimens are also subjected to biochemical analysis, mutational analysis, and electron microscopy, when these techniques are indicated. Inherited myopathies, such as the various muscular dystrophies, are evaluated by immunohistochemical stains, immunoblotting; testing is available for calpain, caveolin, dysferlin, the dystroglycans, dystrophin, laminin-2 (formerly merosin), and the sarcoglycans.

Polymyositis

This inflammatory myopathy is seen mainly in adults and presents subacutely usually over a period of several weeks to a few months. Clinically an important means for distinguishing polymyositis (PM) from dermatomyositis (DM) is the absence of skin involvement in PM. However, DM may also rarely present without skin involvement (sine dermatitis). Various criteria have been proposed to make a definitive diagnosis of PM. Usually PM patients present with symmetric proximal weakness, involving the upper and lower extremities. Mild dysphagia, myalgia, and systemic symptoms, such as polyarthritis, may accompany the weakness. Rarely patients may present with either a clinically isolated head drop, or respiratory muscle weakness. Acid maltase deficiency, glycogen storage disease type II, needs to be considered in those individuals presenting primarily with pulmonary manifestations.

EMG is often abnormal and may show characteristic findings, myopathic motor units, and increased insertional activity, with fibrillation potentials and complex repetitive discharges. Laboratory studies reveal an elevated CK level. Muscle biopsy demonstrates perimysial and endomysial inflammatory infiltrate with CD8+ T cells invading nonnecrotic muscle fibers (see Fig. 76-5). Interstitial lung disease can be seen in 10–20% of patients with PM and may be associated with positive anti-Jo1 antibody. Cardiac involvement (cardiomyopathy and congestive heart failure) is common, although the incidence of these associated conditions is unknown.

Dermatomyositis

Dermatomyositis (DM) is also seen in both children and adults. Proximal weakness develops insidiously over weeks. The characteristic rash may accompany or precede the myopathy (see Fig. 76-1). The rash is present over the exposed areas of the face, neck, and arms. Other dermatologic manifestations include heliotrope rash over the eyelids and erythematous rash over the knuckles, known as Gottron papules (Fig. 76-1, bottom). Nail bed examination will often demonstrate capillary telangiectasia. Occasional DM patients never develop this classic rash; here the differential diagnosis from PM is made on the classic pathologic findings of perifascicular atrophies in the muscle biopsy. In contrast, some patients present with the classic DM rash but paradoxically have no signs of a clinical myopathy (amyopathic DM). Other systemic manifestations include calcinosis, dysphagia, cardiomyopathy, and interstitial lung disease (ILD) (see Fig. 76-4). As in PM, ILD may be associated with positive anti-Jo 1 antibodies in some patients.

Dermatomyositis in adults may be associated with underlying malignancy. The cumulative incidence rate of malignancy varied from 20% at 1-year post DM diagnosis to approximately 30% five years after the diagnosis of DM. Adult patient should undergo evaluation for a possible underlying malignancy. The intensity of diagnostic evaluation for a potential occult cancer is determined individually. Factors that point to a higher likelihood of a paraneoplastic relationship include age at diagnosis >52 years, a rapid onset of skin and/or muscular symptoms, the presence of skin necrosis or periungual erythema, and a low baseline level of complement factor C4. This association with malignancy is not seen in juvenile DM and rarely if ever in polymyositis. A general physical examination, a thorough review of systems, a chest radiograph or computed tomography (CT), a mammogram (in women), a complete blood count (CBC), urinalysis, and stool guaiac, colonoscopy, Pap smears in women, and CT scan of abdomen and pelvis are considered a reasonable screening protocol.

Laboratory tests typically demonstrate the elevated CK. ANA and anti-Jo1 may be elevated. MRI usually shows inflammation in affected muscles. EMG will reveal characteristic myopathic changes in established disease. The characteristic histopathology in DM is perifascicular atrophy although this may not be seen in early disease (see Fig. 76-5). Inflammation is not prominent; when present it is seen in the perimysial and perivascular regions.

The pathogenesis of DM is thought to be a microangiopathy. A membrane attack complex (MAC) can be demonstrated on capillaries. Electron microscopy (EM) may reveal tubuloreticular inclusions in endothelial cells.

Treatment of Polymyositis and Dermatomyositis

Muscle disorders are best managed by considering disease-specific therapies, genetic counseling, and various forms of supportive care. Unfortunately, few specific pharmacologic therapies are currently available for the myopathies. Directed therapies are anticipated for a number of genetic disorders but are not yet available.

Inclusion Body Myositis

Toxic Myopathies

Many pharmacologic agents may cause myopathies as rare adverse effects of their use (Box 76-1). The almost ubiquitously utilized HMG–CoA reductase inhibitor (statin) class of lipid-lowering agents may cause a necrotizing myopathy in a small percentage of these patients. Muscle biopsies in severely affected patients demonstrate necrosis and mitochondrial changes.

More commonly, a slightly larger percentage develops an asymptomatic hyperCKemia. This is thought to be related to subclinical muscle inflammation. On other occasions, some patients taking statins present with myalgias, and/or proximal weakness. Very rarely a rhabdomyolysis may develop in this setting. The risk for muscle toxicity increases in patients simultaneously exposed to multiple potentially myotoxic drugs. Fibric acid derivatives and niacin also occasionally demonstrate myotoxic properties.

Chloroquine may cause an amphiphilic neuromyopathy. These patients classically demonstrate both a peripheral neuropathy and a myopathy. This combination is very typical for chloroquine per se and the physician always needs to inquire about the possibility of the patient utilizing this medication. The serum CK level is often modestly increased in this setting. Muscle biopsy characteristically reveals an autophagic vacuolation, with markedly increased staining for acid phosphatase.

Chronic administration of steroids, typically at doses higher than 30 g/day, can also cause a myopathy. Steroid myopathy can present acutely or subacutely, classically with preferential involvement of the proximal lower extremities. Bulbar and distal muscles, sensation, and reflexes are typically spared. Importantly, CK is normal. Nerve conduction and needle EMG are typically normal, and muscle biopsy may demonstrate atrophy of type II (especially IIB) fibers, lipid droplets within type I fibers, and rarely abnormal mitochondria on electron microscopy.

Amiodarone is an antiarrhythmic drug that causes a neuromyopathy similar to that produced by chloroquine. It can also cause myopathy indirectly, by inducing hypothyroidism.

Colchicine may also cause either a myopathy or neuropathy, which may be related to colchicine-induced alteration of microtubular function. CK is usually increased, and muscle biopsies demonstrate autophagic vacuoles. Symptoms improve with drug discontinuation.

Immunosuppressive agents including cyclosporine and Tacrolimus may cause generalized myalgias and proximal muscle weakness within months after starting therapy. The pathogenic basis for this effect is still unknown; there is some suggestion that cyclosporine myotoxicity may have a pathogenesis similar to that of statins. There is a further increased risk of developing a myopathy when patients take both cyclosporine and statins.

Labetalol is an antihypertensive drug that has been associated with rare reports of necrotizing myopathy. Symptoms improve after discontinuation of the drug.

Propofol is a relatively newer anesthetic agent increasingly used in sedating ventilated patients. There have been reports of rhabdomyolysis and myoglobinuria described in children, but not in adults. Vincristine, a chemotherapeutic agent, acts by disrupting the polymerization of tubulin into microtubules. It is classically associated with a severe sensorimotor axonal neuropathy, but occasionally it can also cause proximal muscle weakness accompanied by myalgias.

Zidovudine (AZT), a primary therapy for HIV infection, can induce a myopathy related to mitochondrial dysfunction. The myopathies caused by zidovudine and by HIV infection are clinically indistinguishable. CK values are usually increased. EMG does not distinguish between toxic AZT and HIV myopathies. Muscle biopsies demonstrate endomysial inflammation. Prominent ragged red fibers suggest AZT-induced mitochondrial abnormalities. AZT myopathies usually improve on drug cessation.

Critical Illness Myopathy

Critical illness myopathy (CIM) is also referred to as acute quadriplegic myopathy or myopathy associated with thick filament (myosin) loss. It is probably the most common cause of generalized weakness identified for patients having a prolonged stay in the ICU. CIM is commonly seen in patients treated with high doses of corticosteroids or neuromuscular blocking drugs. Often these patients were initially septic and developed multiorgan failure. It may be associated with a sensorimotor axonal polyneuropathy (critical illness neuropathy).

The weakness in these patients develops over several days. It is often not recognized until there is an attempt to wean the patient from their ventilator. Clinical examination reveals a profound, occasionally asymmetric, weakness, with reduced muscle stretch reflexes, but a normal sensory examination. Serum CK is increased in less than half of these patients. Muscle biopsies may demonstrate muscle fiber necrosis, atrophy of type 1 and 2 fibers, and patchy loss of uptake with adenosine triphosphatase stains; the latter correlates with electron microscopic demonstration of thick filament (myosin) loss. The pathogenesis of this entity is not known.

Hypokalemic Myopathies

Hypokalemia is a rare metabolic cause of an acute myopathy (Fig. 76-8). The presentation may mimic Guillain–Barré syndrome. ICU observation is recommended because of potential serious cardiac arrhythmias that the severe hypokalemia may induce. The differential diagnosis includes various potassium-losing diuretics and corticosteroids and other medications (e.g., laxatives, lithium, or amphotericin). Chronic alcoholism, rarely hyperaldosteronism or a villous adenoma of the colon, and very excessive intakes of licorice, are other important causes of hypokalemia-induced weakness.

Figure 76-8 Hypokalemia Associated Myopathy.

Endocrine Myopathies

Clinical Vignette

A 41-year-old woman had typical myopathic symptoms. Her husband noted that her emotions were more labile. Neurologic examination demonstrated moderate proximal weakness. Serum CK was normal but the aldolase was mildly elevated. When she returned for her EMG, the neurologist noted generalized bruising that resembled that of patients taking corticosteroids, although neither was she taking same nor were there any apparent other common stigmata of Cushing syndrome. The patient’s EMG demonstrated myopathic motor unit potentials with fibrillation potentials.

Because of her obvious classic dermatologic stigmata, Cushing syndrome was considered in the differential of this slowly evolving myopathy. Serum cortisol and particularly urinary free cortisol levels as well as 24-hour 17-OH corticosteroids were increased. An endocrinologist also found historical evidence of easy bruising, and recent-onset hypertension; this exam demonstrated very mild increase in facial hair, slight mooning of her facies, but no abdominal striae or shoulder hump. Elevated ACTH levels led to the diagnosis of a corticotrophin-producing pituitary tumor.

Comment: This patient’s clinical picture was suggestive of a proximal myopathy and the easy bruising on examination led to the suspicion of Cushing syndrome. Clinically the typical features of Cushing syndrome were quite subtle. Her EMG findings were surprising because most endocrine myopathies, including corticosteroid-induced myopathies, are not associated with myopathic MUPs or abnormal insertional activity. Despite such, laboratory tests confirmed the diagnosis of Cushing disease.

Disorders of the adrenal, thyroid, parathyroid, and pituitary glands can result in subacute or, less commonly, acute myopathies. Interestingly, muscle involvement in such conditions may be apparent before patients develop typical clinical findings of their primary endocrinopathy. This is well illustrated by the prior vignette.

Cushing syndrome due to hyperadrenocorticism is either primary, iatrogenic, or rarely secondary to excessive pituitary secretion of ACTH (Fig. 76-9). This is one of the more common causes of an endocrine myopathy. Patients with Cushing syndrome, irrespective of etiology, experience proximal muscle weakness with atrophy usually starting in the hip girdles. Distal, bulbar, and ocular muscles are usually unaffected. Women seem to be more susceptible than men. Alternate-day corticosteroid dosing schedules and enriched protein diets may reduce susceptibility to iatrogenic induced Cushing syndrome. The serum CK level is usually normal. EMG is normal in iatrogenic steroid myopathy but is occasionally “myopathic” in patients with true Cushing syndrome. Muscle biopsy demonstrates a nonspecific type II muscle fiber atrophy. The pathogenesis of the myopathy is poorly understood but may be related to increased protein catabolism.

Figure 76-9 Cushing (hypercortisolism) and Addison (hypocortisolism) Syndrome.

Primary adrenocortical insufficiency or Addison disease may be associated with a myopathy. Addison disease is characterized by weight loss, bronzing of the skin, hypotension, and hyperkalemia (see Fig. 76-9). Muscle weakness may be an early symptom of this disease and may be due to the associated hyperkalemia.

Thyroid dysfunction is another important consideration in the differential diagnosis of adult-onset myopathies. Hypothyroidism-associated myopathy is characterized by proximal weakness, fatigue, slowed movements and reflexes, stiffness, myalgia, and muscle cramps (Fig. 76-10). An elevated CK, sometimes up to 10 times normal, is a common finding in hypothyroid patients.

Figure 76-10 Hypothyroidism.

Hyperthyroidism-induced myopathy may also present with weakness, and the incidence of weakness in patients with thyrotoxicosis is high (up to 82%). Patients with thyrotoxicosis tend to have proximal muscle weakness and fatigue as prominent complaints (Fig. 76-11). Serum enzyme levels including CPK and AST tend to be normal.

Figure 76-11 Hyperthyroidism (Graves Disease).

In addition to typical myopathic features, hyperthyroid patients have brisk muscle stretch reflexes, thyroid eye disease with proptosis, and impairment of extraocular muscle function. Furthermore, myasthenia gravis occurs in approximately 5% of thyrotoxic patients. Asian males with hyperthyroidism also have a propensity to hypokalemic periodic paralysis. Serum CK and routine electrodiagnostic study results are usually normal.

Hyperparathyroidism may be associated with a painful myopathy. This most likely relates to an interchange with vitamin D metabolism and resultant osteomalacia.

Osteomalacia, Hypovitamin D Myopathy

Lack of vitamin D can lead to decreased calcium and phosphorus absorption and secondary hyperparathyroidism with eventual osteomalacia. This is associated with an unusual but very treatable myopathy with associated bone pain, loss of appendicular height, and kyphoscoliosis.

Although usually considered in chronic renal failure, osteomalacic myopathy may also occur in patients receiving long-term treatment with phenytoin or with various malabsorptive syndromes. Individuals taking statins are more prone to developing symptomatic myositis secondary to hypovitaminosis D. Supplementation of same may totally relieve the symptoms of a painful myopathy while continuing to utilize the statin medication. An unusual setting for development of hypovitaminosis D and osteomalacia occurs in societies where women traditionally are almost totally veiled whenever outside of their homes. Serum vitamin D levels may be very low while CK and electrodiagnostic studies are normal. Muscle biopsy, if performed, demonstrates type II fiber atrophy. Vitamin D and calcium supplementation can lead to excellent improvement.

Granulomatous Myopathies

Although patients with sarcoidosis often have granulomas in muscle tissue, most commonly these patients have no clinical evidence of a myopathy. However, when these are symptomatic, focal pain, atrophy, or generalized proximal weakness may be seen. Diagnosis usually requires involvement of other end organs typically involved by sarcoidosis, particularly the liver or lungs. Nonspecific inflammatory granulomatous myopathies are rare, although they may be seen with underlying myasthenia gravis and thymoma. Ocular and bulbar symptoms attributable to myasthenia may accompany proximal weakness.

Eosinophilic Myopathy

This myopathy is usually present as a component of the hypereosinophilic syndrome. The pattern of weakness is indistinguishable from that of the inflammatory myopathies. Systemic features of hypereosinophilic syndrome involve the heart, lungs, skin, kidneys, and gastrointestinal tract.

Infectious Myopathies

Human immunodeficiency virus (HIV) infection may produce a primary inflammatory myopathy with subacute or chronic proximal weakness and myalgia. Typically seen in patients with CD4 counts of less than 200/mm³, HIV myopathy may be difficult to distinguish from polymyositis.

Nonspecific viral syndromes, particularly in relation to the enteric and influenza viruses, often cause significant myalgia in their prodromal phases. An acute relatively specific viral myositis occasionally occurs in children. It presents with prominent calf pain and toe walking. The CK level is usually increased; EMG may demonstrate myopathic changes, and muscle biopsy reveals scattered necrotic and regenerating fibers. The course is self-limiting. Rarely, there may be severe muscle rhabdomyolysis with significant increase of CK, myoglobinuria, and consequent metabolic derangement.

Trichinosis, typically caused by the ingestion of inadequately cooked pork, is the most common parasitic infection of muscle. Some patients have a prodrome of nausea, vomiting, and periorbital edema within days after exposure. Strikingly severe myalgia, weakness, fever, and sometimes encephalopathy then develop. Occasionally, trichinosis causes a chronic myopathy. Typically there is an associated eosinophilic leukocytosis. The serum CK level may be increased. Muscle biopsy sometimes demonstrates organisms and eosinophilic infiltration.

Pyomyositis is a rare primary bacterial infection characterized by a focal myopathy. This is primarily seen in the tropics. It is more common in immunodeficient individuals. A variety of gram-positive and -negative organisms have been associated with this. Muscle pain, tenderness, and fever are prominent. Neutrophilic leukocytosis and bacteremia also occur. CT and MRI of muscle may demonstrate muscle abscesses.

Paraneoplastic Necrotizing Myopathy

Paraneoplastic necrotizing myopathies are rare and are typically associated with lung, gastrointestinal, or adenocarcinoma. They typically present with gradually progressive proximal weakness with or without myalgias. The serum CK level is often increased. Necrotic muscle fibers with “pipestem” arterioles and capillaries with perivascular inflammation are notable histologic findings.

Supportive Therapies

The goal of all treatments is maximization of patient function. Most patients with significant myopathies benefit from the involvement of a physiatrist early in the course of their illness. Rehabilitation specialists are best able to decide what form of support aids, including braces, canes, crutches, walkers, wheelchairs, lift chairs, stair lifts, elevators, bed rails, and lifting devices, are best suited for the individual patient. Lift chairs are beneficial to ambulatory patients with proximal weakness that precludes them from independently rising from a chair. Elevators and stair lifts are valuable when accessing more than one floor. Newer lift systems allow patient transfers with the help of a single individual. Crutches are of limited value for patients with myopathy because of concomitant arm weakness.

Prognosis

Control rather than immediate cure is often the most realistic initial management goal. DM and PM eventually stabilize or achieve a good to excellent remission, but drug therapy may be required for months or years. Patients with IBM usually have a normal lifespan but some require a wheelchair within 10–15 years after diagnosis. Patients with endocrine, metabolic, infectious, toxic, and vitamin D deficiency myopathies that are usually amenable to treatment generally have an excellent prognosis. The prognosis of paraneoplastic necrotizing myopathies is dependent on that of the underlying malignancy.