1 Introduction

Patients with muscle disorders are a diagnostic challenge to physicians, because of the various ways of presentation. A comprehensive approach should be followed systematically in order to reach the correct diagnosis. Weakness is a common symptom among patients including those with central or peripheral nervous systems diseases and those with muscular and/or neuromuscular diseases. Muscle weakness is not only a regular finding in rheumatologic diseases, but in inflammatory myopathies as well. This chapter focuses on skills needed to approach any patient that presents with weakness, specifically proximal myopathy.

In addition to IIM and CTD, proximal myopathy has a wide range of differential diagnosis including drugs, alcohol, thyroid disease, hereditary myopathies, malignancy, and infections. Clinical assessment should aim to distinguish proximal myopathy from other conditions that present with weakness. Patients with proximal myopathy who need prompt attention, like those with cardiac, respiratory, or pharyngeal muscle involvement, should be identified early and quickly.

In this chapter, the aim is to provide a systematic diagnostic approach to adult patients presenting with proximal myopathy. This is an essential step to establish the correct diagnosis in order to conduct the appropriate management.

1.1 Objectives

By the end of this chapter, you will be able to:

  1. 1.

    Identify true muscular weakness by history and physical examination.

  2. 2.

    Construct diagnostic approach to proximal myopathy.

  3. 3.

    Manage a case of inflammatory myopathy.

2 Clinical Presentation of Proximal Myopathy

Myopathies are diseases that primarily affect the muscles and are usually characterized clinically by weakness, fatigue, or stiffness. Symmetrical proximal muscle weakness, wasting, normal sensation, and normal stretch reflexes are classical findings in patients with myopathies particularly in IIM and myopathies associated with CTD. Aching muscle cramps can also occur. Clinical presentations sometimes can be complex, hence the need to follow a comprehensive approach to weakness.

2.1 History

Weakness is a common complaint with different interpretations by patients. The aim of history taking is to try to define what the patient means by “weakness.” The generalized feeling of tiredness and/or fatigability is usually associated with systemic diseases like congestive heart failure, cirrhosis, and anemia. In these patients there is usually a long-standing history of a chronic disease like ischemic heart disease and/or chronic liver disease. The activity in these patients is usually limited by dyspnea, chest pain, joint pain, fever, and/or depressed mood. Long-standing chronic diseases can lead to cachexia with severe muscle atrophy, wasting, and consequent generalized weakness. The sense of generalized tiredness and/or fatigability should be differentiated from the complaints of generalized body aches and pains in patients with fibromyalgia. The generalized body aches and pains have their own approach that is beyond the scope of this chapter.

Once it is established that the weakness is not a consequence of a non-muscular, generalized, systemic disease and there are no generalized body aches and pains, then it is essential to find out whether this weakness is localized to certain areas. Hemiparesis (weakness affecting upper and lower limbs on the same side of the body) should direct the history towards central nervous system diseases like stroke. Paraparesis (weakness of both lower limbs) and/or quadriparesis (weakness of the four body limbs) should limit the differential diagnosis to spinal cord and/or cerebral cortex and/or brain stem diseases. Monoparesis (weakness of one limb) is usually a disease of a peripheral nervous system including disc prolapse causing radiculopathy by compressing on a spinal nerve to peripheral nerve involvement in vasculitis. Figure 9.1 is a schematic that should be followed while obtaining history and examining patients with weakness.

Fig. 9.1
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The four anatomic stations underlying lower motor neuron weakness

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Symmetrical weakness occurs in large number of diseases including inflammatory myositis, inherited muscle dystrophy, endocrine disorders, and neuromuscular junction diseases. In symmetrical and diffuse weakness, it is important to know if the weakness is proximal or distal. There are several clues in the history that point towards proximal myopathy (muscles of the trunk, shoulders, and thighs). The patient will have difficulty combing hair, difficulty climbing up the stairs, difficulty standing from a sitting position, and/or difficulty in getting up from bed. In distal myopathy, the patient will complain about difficulties while performing fine work like handling the objects by hands and driving. These patients may also present with wrist drop or foot drop. It must be noted that there are diseases affecting proximal muscles in an asymmetrical fashion like diabetic amyotrophy as well as diseases with both proximal and distal muscle weakness in symmetrical and/or asymmetrical fashion like in systemic lupus erythematosus (SLE) with myopathy and vasculitis, respectively. Inclusion body myositis, a rare IIM in elderly patients, presents with both proximal and distal myopathies simultaneously. The focus should be simply to identify the localization of the weakness, and then with comprehensive approach to history taking like what is described in Chap. 1, the differential diagnosis should be easier to obtain.

There are special characters for weakness that signify certain alerts to specific diagnoses. Ascending pattern of weakness should direct the attention towards demyelinating diseases like acute inflammatory demyelinating polyneuropathy (Guillain-Barre syndrome). Descending patterns that start centrally and proceed progressively to distal areas should direct the attention to infections like botulism. The weakness that is worsened by repetitive movement at the end of the day with double vision and drooping eyelids should direct the attention towards neuromuscular disorders like myasthenia gravis.

An extensive review of rheumatologic symptoms should follow; this was outlined thoroughly in Chap. 1. Detailed history of joint pain, skin rashes, fever, recent infections, bleeding tendencies, history suggestive of malignancies, and/or drug history (particularly statins and glucocorticoids) should all be obtained. Endocrine disorders should also be ruled out by reviewing common symptoms like neck swelling, diarrhea/constipation, and heat/cold intolerance. Further details are found below. Detailed family history should be obtained as there are several rare hereditary myopathies that run in families (see below). A family history may also be present in other causes of weakness including dermatomyositis, polymyositis, and potassium-related paralyses. A thorough neurological history is important. Sensory deficits, impaired level of consciousness, speech or visual defect, seizure, and sphincter control should be obtained from patients with weakness. In addition, social history will further help narrow the diagnosis; thus, history of smoking, alcohol, illicit drug use, and exposure to toxins like organic phosphorus should be obtained.

There are life-threatening symptoms associated with IIM like dysphagia and nasal regurgitation resulting from skeletal muscle involvement of the pharynx and upper third of the esophagus and/or chest pain and heart failure from cardiac muscle involvement. These should be identified promptly as they need urgent medical intervention. Breathlessness might suggest respiratory muscle involvement. Respiratory failure can occur in some diseases like Guillain-Barre syndrome, myasthenia gravis, and amyotrophic lateral sclerosis. Table 9.1 summarizes some of the common symptoms of diseases presenting with weakness.

Table 9.1 Associated symptoms presented with muscle weakness
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2.2 Physical Examination

The physical examination is an objective confirmation of the distribution and the severity of the muscle weakness. The first step is to observe the patient doing certain activities like raising arms, standing up from a chair, or writing. This will determine if the weakness is proximal, distal, or combined. A comprehensive neurological examination should follow with higher function examination and examination of cranial nerves. You may find ptosis, ophthalmoplegia, and/or poor gag reflex in myasthenia gravis patients. The next step is performing detailed motor examination. This starts with inspection of the muscle bulk and determining whether if it is normal, atrophied, or hypertrophied. In addition to observation for any fasciculation that might suggest LMND, tone, power, reflexes, and gait should also be examined. Clear distinctions between signs of upper motor neuron disease (UMND) (hypertonia, hyperreflexia, and upgoing plantar response) and signs of LMND (for lesions from the anterior horn cell until muscles) (hypotonia, normal or low or absent reflexes, and equivocal or downgoing plantar response) should be made. Usually with signs of UMND, patients may present with hemiparesis, paraparesis, and quadriparesis or with variable locations in the central nervous system as in multiple sclerosis. Since weakness is a prominent sign present in both UMND and LMND, it is essential to assess the power and document the degree of weakness, as well as for proper future monitoring of this disease while on treatment. Clinical approach to weakness is illustrated in Fig. 9.2. Grades of power are shown in Table 9.2.

Fig. 9.2
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Clinical approach to weakness

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Table 9.2 Grades of power
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Reflexes are usually intact in proximal myopathy, and any signs of abnormal reflexes suggest neurological cause. The last step in the neurological examination is examining sensory level. For example, in peripheral neuropathy loss of sensation is parallel to the weakness. After comprehensive neurological examination, a search for extra-muscular signs should follow. The examination of the face, hands, lower limbs, chest, and abdomen is important, since any abnormality can help in the differential diagnosis. Few signs of common diseases presenting with myopathy are shown in Table 9.3.

Table 9.3 Common signs with specific myopathies
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There are certain associations essential to be recognized while performing the physical examination. These associations may easily reveal the diagnosis without spending efforts on unnecessary investigations. Changes in the mental status, for example, with muscle weakness may indicate electrolyte imbalance. Cardiovascular assessment may reveal signs of cardiomyopathy, which is associated with some inflammatory and hereditary myopathies. Pulmonary assessment may reveal crackles of interstitial lung disease associated with some inflammatory myopathies. Lymph node examination is essential as malignancies are associated with a significant number of IID including lymphoma. Small joint examination is essential as well to detect any tenderness and/or swelling suggestive of rheumatoid arthritis (RA) and/or systemic lupus erythematosus (SLE)-associated myopathies. Skin examination is helpful: signs like Gottron’s papules in dermatomyositis, erythema nodosum in sarcoidosis, and skin bronzing in adrenal insufficiency (see Dermatology chapter). Also a search for any signs possibly related to underlying malignancy like finger clubbing, fecal occult blood, and hepatosplenomegaly should be made. Table 9.4 lists findings with their most likely definitive diagnosis. The vital signs should be measured to exclude any life-threatening problems. Postural hypotension can be seen in autonomic neuropathy, e.g., in diabetes mellitus and Lambert-Eaton syndrome. Also, body mass index (BMI) should be measured to assess if the patient is underweight suggestive of a malignant disease process.

Table 9.4 Correlation between findings and suggestive diagnoses of weakness
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3 Differential Diagnosis of Proximal Myopathy

Several conditions cause proximal myopathy. Myopathies can be classified into idiopathic or acquired. The clinical history and physical examination are essential in identifying the presence of a myopathy and narrowing down the differential diagnosis. In adults a major cause of myopathy is medication like statins [1]. Myopathy due to endocrine causes, for example, thyroid disease, Cushing disease, and adrenal diseases, should be diagnosed promptly because treating the primary condition will result in resolution of the myopathy [2]. Inflammatory diseases typically affect older adults including both proximal and steroid responsive disorders like polymyositis and dermatomyositis and distal and proximal myopathies with less response to steroid like inclusion body myositis. Rheumatologic disorders causing weakness, such as SLE and RA, can occur in young and elderly persons. Figure 9.3 summarizes the differential diagnosis of proximal myopathy. Further details about these disorders will be mentioned briefly in this section.

Fig. 9.3
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Differential diagnosis of proximal myopathy

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3.1 Toxins- and Drug-Induced Myopathy

Considering toxin and drug exposure in the differential diagnosis of every single patient presenting with proximal myopathy is essential. The timely diagnosis allows for optimum recovery. There are many drugs that cause proximal myopathy, such as lipid-lowering drugs, glucocorticoids, antimalarial drugs, antiretroviral drugs, alcohol, and cocaine [1]. There is an acute presentation in drug-induced myopathy. Statin therapy associated with muscle problems is seen in approximately 10–25% of patients treated in clinical practice. Statin-induced myopathy can present as myalgia and myositis or sometimes is severe enough to cause rhabdomyolysis. The average onset of statin-induced myopathy is weeks to months. The only treatment is discontinuation of statin which results in resolution of muscle symptoms [3]. Glucocorticoids are a common cause of muscle weakness. Long-term use of glucocorticoids results in an insidious onset of proximal myopathy. Muscle enzymes are usually normal. Relief of the weakness occurs with lowering the dose of glucocorticoids [4]. Alcohol-induced myopathy generally follows a history of long-standing alcohol intake and/or consumption of large amount of alcohol. Table 9.5 summarizes pertinent features of the common causes of toxin- and drugs-induced myopathy.

Table 9.5 Features of toxin- and drug-induced myopathy
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3.2 Endocrine Myopathy

Hormones play an essential role in body metabolism. Deficiency or excess in most hormones will affect muscle metabolism. In endocrine-related muscle diseases, the presentation is more likely to be fatigue than true muscle weakness. The serum CK level is often normal (except in hypothyroidism). Nearly all endocrine myopathies respond to treatment [5].

Abnormalities in thyroid hormone can lead to a wide range of muscle diseases. For example, hypothyroid patients have frequent muscle complaints such as cramps, pain, and weakness. Almost one third of hypothyroid patients present with proximal myopathy. They present mainly with shoulder and hip muscle weakness. Treatment by thyroid replacement usually leads to resolution of symptoms and laboratory abnormalities [6]. Proximal myopathy is a very common presentation in hyperthyroid patients and may be the only symptom of the disease. Bulbar, respiratory, and even esophageal muscles may be affected, causing dysphagia and aspiration. Other neuromuscular disorders may occur in association with hyperthyroidism including hypokalemic periodic paralysis, myasthenia gravis, and a progressive ocular myopathy. Because proximal weakness is a presenting sign of hyperthyroidism and hypothyroidism, checking thyroid-stimulating hormone (TSH) is essential. Adrenal insufficiency causes muscle fatigue rather than true muscle weakness. Conn’s syndrome can lead to proximal myopathy which is related to hypokalemia [7]. Pituitary disorders like acromegaly if long-standing can cause myopathy [8]. Neuromuscular complications of diabetes mellitus (DM) are mainly due to neuropathy which can be presented as asymmetrical proximal weakness. Ischemic infarction of the thigh muscles can present with severely uncontrolled diabetes [9] (see Chap. 21 (Diabetes and Rheumatology)). Table 9.6 summarizes pertinent findings of myopathies caused by endocrine disorders.

Table 9.6 Pathophysiology and characteristics of endocrine myopathies
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3.3 Dystrophic Myopathies

Dystrophic myopathies are a distinct group of inherited muscle disorders that generally present chronically. They are slowly progressive in nature resulting in muscle atrophy with exception of metabolic myopathies, where symptoms on occasion can be precipitated acutely. Each type of dystrophic myopathy has some characteristic structural abnormalities on muscle immunohistochemistry. Congenital myopathies present predominantly in the perinatal period. Some can present later in childhood, and these children may have a milder course of the disease. Multiple gene defects can give rise to similar clinical and ultrastructural phenotypes; thus, muscle immunohistochemistry should be tested to reach a final diagnosis. Table 9.7 shows the features of dystrophic myopathy [10].

Table 9.7 Features of dystrophic myopathy
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3.4 Inflammatory Myopathies

Inflammatory myopathies are a group of complex diseases of unknown etiology. The most common types are dermatomyositis, polymyositis, and inclusion body myositis. Table 9.8 represents the current classification for IIM. The incidence of inflammatory myopathies is 5–10/million cases per year [11]. These diseases are characterized by progressive muscle weakness with extra-muscular organ involvement and high serum muscle enzymes. Generally there is a female predominance 2:1, but in inclusion body myositis, the opposite is seen as it is three times more common in males [12]. The main pathophysiology is related to autoimmunity, though recent studies show that the mechanism of muscle damage is multiple and complex [13].

Table 9.8 Classification of idiopathic inflammatory myopathies
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The clinical features of inflammatory myopathy in general are muscle weakness occurring within weeks to months. The distribution of weakness is mainly proximal in dermatomyositis and polymyositis, but as the disease progresses, distal muscles may become affected. On the other hand, distal muscle weakness is the initial presentation of inclusion body myositis. The onset of polymyositis is usually after the second decade of life. Dermatomyositis has two peaks, the first peak at around 10–15 years of age and the second peak between 40 and 70 years. Inclusion body myositis occurs after the age of 50. Table 9.9 summarizes the pathological and clinical features of the most common IID.

Table 9.9 The pathogenetic mechanisms and clinical features of the most common IID
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Dermatomyositis is known for its cutaneous manifestations. The rashes can precede, follow, or occur simultaneously with the myopathy. Gottron’s papules and heliotrope rash are pathognomonic features of dermatomyositis [14]. Dermatomyositis and polymyositis are also known to cause manifestations related to the cardiovascular system, respiratory system, and gastrointestinal system.

Patients diagnosed with IID tend to have a higher risk of developing malignancies. Patients with dermatomyositis or polymyositis have an increased risk of developing malignancy. Those with dermatomyositis are three to six times more likely and those with polymyositis are two to four times more likely than the normal population to develop ovarian, gastric, pancreatic, and lung cancer and non-Hodgkin lymphoma. Thus screening for malignancies is highly recommended in this population [15].

3.5 Myopathy Due to Infectious Disease

Infectious diseases may cause an acute presentation of weakness with muscle cramps, myoglobinuria, and rhabdomyolysis. Among the infectious causes, viral infections are the most common. Myalgia is the most common symptoms, but can last up to 2–3 weeks. Usually myopathy due to viral infections is self-limiting, but severe cases may cause myoglobinuria and renal impairment.

Human immunodeficiency virus (HIV) is an important differential when approaching myopathy; the condition is often referred to as HIV polymyositis. HIV polymyositis can be a presenting manifestation of HIV infection or can occur in later stages. Patients with HIV polymyositis may present with asymptomatic elevation of CK levels, or as severe muscle tenderness and muscle weakness. HIV-related myopathy appears to have a better prognosis than idiopathic inflammatory myopathies. See the treatment section for how to manage HIV polymyositis.

4 Diagnostic Approach

A thorough history and physical examination is the cornerstone to reach the diagnosis. Investigations should be tailored to screen for reversible causes of a myopathy (Fig. 9.4).

Fig. 9.4
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Approach to statin-induced myopathy

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When the cause of muscle weakness is unclear, appropriate testing should be performed, and it is recommended to start with blood tests including electrolytes (potassium, calcium, phosphate, and magnesium), thyroid-stimulating hormone (TSH) level, alkaline phosphatase and 25 (OH) vitamin D level, and HIV [16].

4.1 Muscle Enzyme

The measurement of serum levels of muscle enzymes is of critical value for the evaluation and monitoring of muscular disorders. Creatine kinase (CK), lactate dehydrogenase (LD), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and aldolase are the serum muscle enzymes that are measured in clinical practice. In patients with suspected myopathy who do not demonstrate CK elevation, testing for aldolase can be helpful, but it is less sensitive and less specific [17].

Approach to high level of CK is demonstrated thoroughly in Table 9.10. It must be noted that CK elevation is, however, not specific to myopathy and further testing should be performed in a comprehensive approach. Table 9.11 shows the differential diagnosis to high CK level.

Table 9.10 Approach to high CK level
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Table 9.11 Differential diagnosis to high CK level
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While diagnosing myocardial infarction, besides symptoms and abnormal ECG findings, there will be rise in CK-MB, the isoenzyme of CK, electrophoretically distinguished and high in concentration in the cardiac tissue. However, it is neither specific nor sensitive as troponins [18].

CK might be falsely elevated secondary to ethnicity (can be high in Afro-Caribbean men), exercise (can remain elevated for up to 72 h), intramuscular injections, needle electromyography (EMG), medications, hypothyroidism, and motor neuron disease [16].

4.2 Rhabdomyolysis

Muscle injury due to vigorous exercise, medication, infection, and metabolic derangements can cause rhabdomyolysis. Severe myalgia, weakness, and red to brown urine due to myoglobinuria are classical initial presenting features. Rise of CK levels is typically seen after 2–12 h of injury and reaches its maximum within 24–72 h. A decline is usually seen within 3–5 days of cessation of muscle injury. Myoglobinuria is present in 50–75% of patients at the time of initial evaluation. Thus it is recommended to perform routine dipstick urine analysis in any patient with extremely elevated CK level and myopathy. There are serious metabolic derangements that complicate this massive muscle destruction in the body. Electrolyte imbalance and acute renal failure are serious examples.

4.3 Other Tests

In addition to CK, to diagnose rheumatologic myopathy, erythrocyte sedimentation rate (ESR) C-reactive protein (CRP), antinuclear antibody assay (ANA), rheumatoid factor, anti-double-stranded DNA, antiphospholipid antibodies, and anti-centromere antibodies should be ordered. In case of inflammatory myopathy, check for anti-Jo1 antibody, directed against histidyl-tRNA synthetase. Recognition of anti-Jo1 syndrome is important because such patients can develop extra-muscular features, such as interstitial lung disease, Raynaud’s phenomenon, and arthritis [19].

4.4 Electromyography (EMG)

Electromyography (EMG) is a test that is used to record muscle electrical activity and assess the nerves that control the muscles. An abnormal electromyogram can indicate a neuropathy or neuromuscular disease. Characteristic EMG findings of myopathy include short duration and decreased amplitude of action potential unlike neuropathies that are characterized by increased duration and amplitude of action potential. Although there are no pathognomonic features that distinguish different forms of myopathy, EMG can help distinguish inflammatory from non-inflammatory forms of myopathy. Normal EMG examination, however, would not exclude myopathy [18]. In case of polymyositis, the site of muscle biopsy should be opposite to where the EMG was conducted [16].

4.5 Muscle Magnetic Resonance Imaging (MRI)

MRI evaluates deep muscles not readily accessible by EMG and plays a role in the diagnostic process by identifying subclinical signs of muscle involvement. Fat-suppressed and short tau inversion recovery techniques differentiate between active myositis, pictured as edema, and chronic inactive myositis in patients with inflammatory myopathy, presented as fat [20]. A secondary role for muscle MRI is to provide information about the best site for muscle biopsy by showing which muscles are involved in the myopathic process.

4.6 Muscle Biopsy

Establishing the diagnosis of IID is essentially based on histopathological grounds. There are currently advanced therapies that can be used effectively in these patients. The justification of using these drugs or even steroids should be based on muscle biopsy. Open surgical biopsy is preferable to closed needle biopsy because of the patchy nature of inflammation in PM and so that adequate tissue could be obtained. However, in some circumstances, the biopsy is performed by expert radiologists. Muscle biopsy is a reliable instrument in the diagnosis of PM in 85% of the patients [18]. It is an outpatient procedure that may cause pain, bleeding, infection, or sensory loss. No special preparation is required other than that patients should discontinue using anticoagulants before the procedure [21].

The best muscles to biopsy are those moderately affected by the disease process but not atrophied. Previous sites of injections, EMG examination, or trauma should be avoided. The most common biopsy sites are the deltoid, quadriceps for proximal myopathy, and gastrocnemius for distal myopathies.

Technology using genetic markers is advancing rapidly. In inflammatory myopathies, immune staining for major histocompatibility classes I and II (MHC-I/II) is upregulated in myofibrils, whereas MHC-I immune staining alone is non-specific [22].

4.7 Screening for Malignancy

Idiopathic inflammatory myopathies PM and DM have positive relation to malignancy; retrospective studies’ results justify CT of the chest, abdomen, and pelvis in addition to age-appropriate screening tests such as colonoscopy and mammography for any patient newly diagnosed. This is shown in Southeast Asia where input of otolaryngologists is invaluable due to the higher incidence of nasopharyngeal carcinoma for DM patients. Recent advances in understanding of pathogenesis of idiopathic inflammatory myopathies have led to discovery of biomarkers like type 1 interferon and myeloid cell signatures to distinguish active disease from chronic injury [17].

4.8 Genetic Testing

Genetic testing is becoming increasingly useful in confirmation of patient with muscular dystrophies and heritable myopathies. These mutations can be identified through peripheral blood DNA analysis. Molecular testing often eliminates the need for muscle biopsy.

5 The Management of Myopathy

5.1 Inherited Myopathy

For most patients with congenital myopathy or muscular dystrophy, the treatment is mainly supportive. Physical therapy, occupational therapy, management of contractures, nutrition, and genetic counseling together play a role in managing congenital myopathies. In patients with Duchenne muscular dystrophy, treatment with prednisone has been shown to improve strength and muscle bulk and slow the rate of natural progression of the disease. Patients should also be monitored over time for complications related to kyphoscoliosis or involvement of cardiac, respiratory, or bulbar muscles. Finally, genetic counseling should be offered to all patients with inherited myopathy and their family members.

5.2 Acquired Myopathy

Management of proximal myopathy depends on underlying etiology. Treatable causes should be sought and treated accordingly. Discontinuation of offending drug is likely to improve symptoms in patients with drug-induced myopathy, e.g., statins [5]. Dose reduction should be considered for those patients in whom abrupt discontinuation of drug may not be possible, e.g., steroid myopathy [6]. In HIV-related myositis, treatment with the combination of highly active antiretroviral therapy (HAART) and steroids may be beneficial.

Treatment of IIM is largely empirical because of paucity of well-controlled trials. Current evidence is mostly based on retrospective or open prospective trials involving small numbers of patients. Corticosteroids are the cornerstone in the treatment of PM and DM [19, 20]. In the absence of placebo-controlled trials, the optimal initial dose and duration of therapy are uncertain, but patients are generally started on 0.75–1 mg/kg body weight/day of prednisolone. Intravenous pulse methylprednisolone is initially considered for those with cardiac, respiratory, or pharyngeal muscle involvement to obtain quicker response. Because maximal improvement may not be seen for several weeks, the usual practice is to start tapering the dose of prednisolone only after about 4–12 weeks, guided by clinical improvement. Many patients relapse when corticosteroids are discontinued, and therefore, a maintenance dose of 5–10 mg/day is often required for several years. About a third of patients with PM or DM, and those with IIM, might fail to show any response to prednisolone. Second-line immunosuppressive drugs are tried in patients who do not respond to corticosteroids alone and in those with progressive disease and internal organ involvement. Choice of drug is largely empirical and depends on disease severity, extra- muscular manifestations, and personal experience of treating physician, again because of paucity of well-conducted trials.

Azathioprine [23] or methotrexate is usually preferred. Intravenous immunoglobulin (Ig), the only agent for which there is positive evidence from randomized placebo-controlled trial [21, 24], is especially useful for patients with dysphagia and treatment-resistant DM. Intravenous Ig is, however, expensive and limited in availability. Cyclophosphamide, given as monthly intravenous pulses for 3–6 months, is also an option for patients with respiratory muscle weakness, interstitial lung disease, or cardiac involvement [25]. Plasmapheresis has also been studied, but was not found to be helpful in a double-blind placebo-controlled trial [26]. Rituximab, a CD20 monoclonal antibody that depletes B cells, has been reported to have a favorable effect in small open-label uncontrolled trials [27, 28]. A new double-blind, placebo-phase trial in refractory adult and pediatric myositis using rituximab revealed good results [29]. Tumor necrosis factor inhibitors such as infliximab, adalimumab, and etanercept are ineffective in treating IID and may cause deterioration or trigger the disease [30]. Other biological agents that may be considered as experimental treatments include alemtuzumab, which is reportedly effective in polymyositis [31], and anti-complement C3 (eculizumab), which may be effective for the treatment of dermatomyositis. Overall, the long-term outcome of inflammatory myopathies has substantially improved, with a 10-year survival rate of more than 90% . Table 9.12 shows a step-by-step approach in the management of IID [32].

Table 9.12 Approach to treatment of inflammatory myopathies
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Input of physiotherapist is also valuable because randomized controlled trials among patients with IIM have demonstrated that exercise therapy, adapted to the patient’s condition, is beneficial and safe [33]. Benefits of exercise not only include improved muscle endurance, strength, and functional abilities but also prevent muscle wasting and fibrotic contractures.