Introduction
Muscle disorders present a significant diagnostic challenge to healthcare professionals due to their diverse clinical presentations. A systematic and thorough approach is crucial to achieve an accurate diagnosis. Weakness is a prevalent symptom experienced by patients across various conditions, including diseases affecting the central and peripheral nervous systems, as well as muscular and neuromuscular disorders. Furthermore, muscle weakness is a common manifestation in rheumatologic diseases, notably in inflammatory myopathies. This guide focuses on the essential skills required to evaluate patients presenting with weakness, specifically addressing proximal myopathy and its differential diagnosis.
Proximal myopathy, characterized by weakness in muscles closer to the center of the body such as hips, shoulders, and upper arms, requires careful differentiation from other conditions that manifest as generalized weakness. The range of potential diagnoses is broad, encompassing inflammatory myopathies (IIM), connective tissue diseases (CTD), drug-induced myopathies, alcohol-related myopathy, thyroid disorders, hereditary myopathies, malignancies, and infections. Early identification of patients with proximal myopathy who require immediate attention, such as those with involvement of cardiac, respiratory, or pharyngeal muscles, is paramount for timely intervention.
This guide aims to provide a structured and systematic diagnostic approach for adult patients presenting with proximal myopathy. Establishing a correct diagnosis is the crucial first step in determining appropriate management and treatment strategies.
Objectives
Upon completion of this guide, you will be able to:
- Distinguish true muscular weakness from other causes of perceived weakness through detailed history taking and physical examination.
- Develop a structured diagnostic approach to proximal myopathy.
- Understand the management strategies for inflammatory myopathies.
Clinical Presentation of Proximal Myopathy
Myopathies are a group of diseases that primarily affect the muscles, typically characterized by symptoms such as weakness, fatigue, and muscle stiffness. A hallmark of myopathies, particularly inflammatory myopathies (IIM) and myopathies associated with connective tissue diseases (CTD), is symmetrical proximal muscle weakness combined with muscle wasting, normal sensation, and normal stretch reflexes. Patients may also experience aching muscle cramps. Given the complexity of clinical presentations, a systematic approach to evaluating weakness is essential for accurate diagnosis.
History
Weakness is a common complaint, but its interpretation can vary significantly among patients. The initial goal of history taking is to clarify what the patient means by “weakness.” A generalized feeling of tiredness or fatigability is often associated with systemic diseases like congestive heart failure, liver cirrhosis, and anemia. These patients typically have a long-standing history of chronic conditions such as ischemic heart disease or chronic liver disease. Their activity levels are often limited by symptoms such as dyspnea (shortness of breath), chest pain, joint pain, fever, or depressed mood. Chronic diseases can also lead to cachexia, a condition characterized by severe muscle atrophy and wasting, resulting in generalized weakness. It is important to differentiate this generalized tiredness from the generalized body aches and pains experienced by patients with fibromyalgia, which requires a distinct diagnostic approach beyond the scope of this discussion.
Once systemic, non-muscular causes of generalized weakness and fibromyalgia-related pain are excluded, it’s crucial to determine if the weakness is localized to specific areas of the body. Hemiparesis, or weakness affecting the upper and lower limbs on one side of the body, suggests central nervous system conditions like stroke. Paraparesis (weakness of both lower limbs) or quadriparesis (weakness of all four limbs) narrows the differential diagnosis to diseases of the spinal cord, cerebral cortex, or brainstem. Monoparesis, or weakness in a single limb, is typically indicative of peripheral nervous system issues, such as disc prolapse causing radiculopathy due to spinal nerve compression, or peripheral nerve involvement in vasculitis. Figure 9.1 provides a schematic guide for history taking and physical examination in patients presenting with weakness.
Fig. 9.1: Anatomic stations illustrating potential sites of lower motor neuron weakness, critical for localizing the origin of muscle weakness symptoms.
Symmetrical weakness, affecting both sides of the body equally, is observed in a range of conditions including inflammatory myositis, inherited muscle dystrophies, endocrine disorders, and neuromuscular junction diseases. In cases of symmetrical and diffuse weakness, it is important to distinguish between proximal and distal weakness. Historical clues can point towards proximal myopathy, affecting muscles of the trunk, shoulders, and thighs. Patients with proximal myopathy may report difficulty with activities like combing hair, climbing stairs, rising from a seated position, or getting out of bed. In contrast, distal myopathy, affecting muscles further from the body’s center, is characterized by complaints of difficulty with fine motor tasks such as handling small objects or driving. Patients with distal myopathy may also present with wrist drop or foot drop. It is important to note that some conditions, such as diabetic amyotrophy, can cause asymmetrical proximal muscle weakness, while others, like systemic lupus erythematosus (SLE) with myopathy and vasculitis, can present with both proximal and distal muscle weakness in symmetrical or asymmetrical patterns. Inclusion body myositis, a less common inflammatory myopathy in older adults, can manifest with both proximal and distal myopathies simultaneously. The primary focus should be on identifying the location of weakness, which, combined with a comprehensive history, will facilitate a more accurate differential diagnosis.
Certain patterns of weakness can suggest specific diagnoses. An ascending pattern of weakness should raise suspicion for demyelinating diseases like Guillain-Barre syndrome (acute inflammatory demyelinating polyneuropathy). Descending patterns, starting centrally and progressing distally, may indicate infections such as botulism. Weakness that worsens with repetitive movement and towards the end of the day, accompanied by double vision (diplopia) and drooping eyelids (ptosis), is suggestive of neuromuscular disorders like myasthenia gravis.
A detailed review of rheumatologic symptoms is essential. This includes inquiring about joint pain, skin rashes, fever, recent infections, bleeding tendencies, history suggestive of malignancies, and medication history, particularly focusing on statins and glucocorticoids. Endocrine disorders should also be considered, and symptoms like neck swelling, diarrhea or constipation, and heat or cold intolerance should be explored. A thorough family history is important as several rare hereditary myopathies have familial patterns. Family history may also be relevant in other causes of weakness, including dermatomyositis, polymyositis, and potassium-related paralyses. A comprehensive neurological history is crucial, including assessment for sensory deficits, altered level of consciousness, speech or visual disturbances, seizures, and sphincter control issues. Social history, including smoking, alcohol consumption, illicit drug use, and exposure to toxins like organophosphates, can further refine the differential diagnosis.
Life-threatening symptoms associated with inflammatory myopathies, such as dysphagia (difficulty swallowing) and nasal regurgitation due to pharyngeal and upper esophageal muscle involvement, or chest pain and heart failure from cardiac muscle involvement, require prompt identification and urgent medical intervention. Breathlessness may indicate respiratory muscle involvement. Respiratory failure is a potential complication in conditions like Guillain-Barre syndrome, myasthenia gravis, and amyotrophic lateral sclerosis (ALS). Table 9.1 summarizes common symptoms associated with diseases presenting with muscle weakness.
Table 9.1: Common symptoms associated with muscle weakness, aiding in the differential diagnosis of various neuromuscular conditions.
Physical Examination
The physical examination provides objective confirmation of the distribution and severity of muscle weakness. Observing the patient performing activities like raising their arms, standing from a chair, or writing helps determine if the weakness is proximal, distal, or combined. A complete neurological examination should follow, including assessment of higher functions and cranial nerves. Findings such as ptosis, ophthalmoplegia (paralysis of eye muscles), and poor gag reflex may be present in patients with myasthenia gravis. A detailed motor examination is the next step, starting with inspection of muscle bulk to assess for atrophy (muscle wasting) or hypertrophy (muscle enlargement). Fasciculations (muscle twitching), which may suggest lower motor neuron disease (LMND), muscle tone, power, reflexes, and gait should also be evaluated. Distinguishing between signs of upper motor neuron disease (UMND) – hypertonia (increased muscle tone), hyperreflexia (overactive reflexes), and upgoing plantar response (Babinski sign) – and signs of LMND – hypotonia (decreased muscle tone), normal, reduced, or absent reflexes, and downgoing or equivocal plantar response – is crucial. UMND signs may be seen in conditions like multiple sclerosis, presenting with hemiparesis, paraparesis, quadriparesis, or variable patterns of weakness depending on the central nervous system lesion location. As weakness is a prominent feature in both UMND and LMND, documenting the degree of weakness is essential for diagnosis and for monitoring disease progression and treatment response. Figure 9.2 illustrates a clinical approach to evaluating weakness, and Table 9.2 outlines the grades of muscle power.
Fig. 9.2: Clinical approach flowchart for evaluating muscle weakness, guiding diagnostic steps from initial presentation to specific investigations.
Table 9.2: Muscle power grading scale used in physical examinations to quantify the severity of muscle weakness.
Reflexes are typically intact in proximal myopathy; abnormal reflexes suggest a neurological cause. The final step in the neurological examination is assessing sensory function. For example, in peripheral neuropathy, sensory loss often parallels the distribution of weakness. Following the neurological examination, a search for extra-muscular signs is important. Examination of the face, hands, lower limbs, chest, and abdomen may reveal abnormalities that aid in differential diagnosis. Table 9.3 lists signs associated with common myopathies.
Table 9.3: Common clinical signs associated with specific myopathies, assisting in narrowing down the differential diagnosis during physical examination.
Recognizing certain associations during physical examination can be key to diagnosis, potentially obviating the need for extensive investigations. Changes in mental status accompanied by muscle weakness may indicate electrolyte imbalances. Cardiovascular assessment may reveal signs of cardiomyopathy, which is associated with some inflammatory and hereditary myopathies. Pulmonary assessment may reveal crackles indicative of interstitial lung disease, seen in some inflammatory myopathies. Lymph node examination is essential as malignancies are associated with a significant proportion of idiopathic inflammatory myopathies (IIM), including lymphoma. Small joint examination can detect tenderness or swelling suggestive of rheumatoid arthritis (RA) or systemic lupus erythematosus (SLE)-associated myopathies. Skin examination is also helpful, with signs like Gottron’s papules in dermatomyositis, erythema nodosum in sarcoidosis, and skin bronzing in adrenal insufficiency being diagnostically relevant. Additionally, look for signs potentially related to underlying malignancy, such as finger clubbing, fecal occult blood, and hepatosplenomegaly. Table 9.4 correlates clinical findings with suggestive diagnoses of weakness. Vital signs should be measured to rule out life-threatening conditions. Postural hypotension may be seen in autonomic neuropathy, for example, in diabetes mellitus and Lambert-Eaton syndrome. Body mass index (BMI) should be assessed to identify underweight patients, which may suggest an underlying malignancy.
Table 9.4: Correlation between clinical findings and suggestive diagnoses of weakness, guiding clinicians towards potential underlying conditions.
Differential Diagnosis of Proximal Myopathy
Proximal myopathy can arise from a variety of conditions, broadly categorized as idiopathic or acquired myopathies. Clinical history and physical examination are crucial in identifying the presence of a myopathy and narrowing the differential diagnosis. In adults, medication, particularly statins, is a major cause of myopathy [1]. Endocrine causes, such as thyroid disease, Cushing’s disease, and adrenal diseases, should be considered and promptly diagnosed because treating the underlying endocrine condition often resolves the myopathy [2]. Inflammatory myopathies are more common in older adults and include steroid-responsive disorders like polymyositis and dermatomyositis, as well as inclusion body myositis, which is less responsive to steroids and can affect both proximal and distal muscles. Rheumatologic disorders like SLE and RA can cause weakness in both younger and older individuals. Figure 9.3 summarizes the differential diagnosis of proximal myopathy. Further details about these disorders are discussed below.
Fig. 9.3: Differential diagnosis flowchart for proximal myopathy, outlining major categories of conditions to consider during diagnostic evaluation.
Toxins- and Drug-Induced Myopathy
Considering toxin and drug exposure is essential in the differential diagnosis of proximal myopathy in every patient. Timely diagnosis allows for optimal recovery upon cessation of the offending agent. Many drugs can induce proximal myopathy, including lipid-lowering drugs, glucocorticoids, antimalarial drugs, antiretroviral drugs, alcohol, and cocaine [1]. Drug-induced myopathy can present acutely. Statin-associated muscle problems are observed in approximately 10–25% of patients treated with statins in clinical practice. Statin-induced myopathy can manifest as myalgia (muscle pain) and myositis (muscle inflammation), or in severe cases, as rhabdomyolysis (muscle breakdown). The onset of statin-induced myopathy typically occurs within weeks to months of starting treatment. Discontinuation of the statin is usually sufficient to resolve muscle symptoms [3]. Glucocorticoids are another common cause of muscle weakness, with long-term use leading to an insidious onset of proximal myopathy. Muscle enzyme levels are typically normal in glucocorticoid-induced myopathy. Reducing the glucocorticoid dose usually alleviates the weakness [4]. Alcohol-induced myopathy is generally associated with a history of chronic alcohol intake or binge drinking. Table 9.5 summarizes key features of common toxin- and drug-induced myopathies.
Table 9.5: Key features of toxin and drug-induced myopathies, highlighting causative agents, presentation, and diagnostic clues.
Endocrine Myopathy
Hormones play a critical role in body metabolism, and both hormone deficiency and excess can affect muscle metabolism. In endocrine-related muscle diseases, fatigue is often more prominent than true muscle weakness. Serum creatine kinase (CK) levels are often normal, except in hypothyroidism. Most endocrine myopathies are reversible with treatment of the underlying endocrine disorder [5].
Thyroid hormone abnormalities can lead to a wide spectrum of muscle diseases. Hypothyroid patients frequently experience muscle complaints such as cramps, pain, and weakness. Proximal myopathy is present in almost one-third of hypothyroid patients, mainly affecting shoulder and hip muscles. Thyroid hormone replacement therapy usually resolves symptoms and laboratory abnormalities [6]. Proximal myopathy is also a common presentation in hyperthyroid patients and may be the sole symptom. Bulbar (muscles controlling swallowing and speech), respiratory, and esophageal muscles can be affected, leading to dysphagia and aspiration. Other neuromuscular disorders, such as hypokalemic periodic paralysis, myasthenia gravis, and progressive ocular myopathy, can co-occur with hyperthyroidism. Given that proximal weakness is a presenting sign of both hyperthyroidism and hypothyroidism, checking thyroid-stimulating hormone (TSH) levels is essential. Adrenal insufficiency typically causes muscle fatigue rather than true muscle weakness. Conn’s syndrome (primary hyperaldosteronism) can lead to proximal myopathy secondary to hypokalemia (low potassium levels) [7]. Pituitary disorders like long-standing acromegaly can also cause myopathy [8]. Neuromuscular complications of diabetes mellitus (DM) are primarily due to neuropathy, which can manifest as asymmetrical proximal weakness. Ischemic infarction of thigh muscles can occur in severely uncontrolled diabetes [9]. Table 9.6 summarizes pertinent findings in myopathies caused by endocrine disorders.
Table 9.6: Pathophysiology and characteristics of endocrine myopathies, detailing hormonal imbalances and their muscular manifestations.
Dystrophic Myopathies
Dystrophic myopathies are a distinct group of inherited muscle disorders generally presenting chronically and progressing slowly. Muscle atrophy is a common feature, except in metabolic myopathies where symptoms can sometimes present acutely. Each type of dystrophic myopathy has characteristic structural abnormalities identifiable through muscle immunohistochemistry. Congenital myopathies typically present in the perinatal period or later in childhood, with milder forms manifesting later. As multiple gene defects can result in similar clinical and ultrastructural phenotypes, muscle immunohistochemistry is crucial for definitive diagnosis. Table 9.7 outlines the features of dystrophic myopathies [10].
Table 9.7: Features of dystrophic myopathies, including inheritance patterns, typical onset age, and characteristic clinical presentations.
Inflammatory Myopathies
Inflammatory myopathies (IIM) are a group of complex diseases of unknown cause. The most common types are dermatomyositis, polymyositis, and inclusion body myositis. Table 9.8 presents the current classification of IIM. The incidence of inflammatory myopathies is approximately 5–10 cases per million people per year [11]. These diseases are characterized by progressive muscle weakness, extra-muscular organ involvement, and elevated serum muscle enzymes. Generally, there is a female predominance (2:1), except for inclusion body myositis, which is three times more common in males [12]. Autoimmunity is considered the main underlying mechanism, although recent research suggests a more complex and multifactorial pathogenesis of muscle damage [13].
Table 9.8: Classification of idiopathic inflammatory myopathies, categorizing subtypes based on clinical and pathological features.
The clinical presentation of inflammatory myopathy typically involves muscle weakness developing over weeks to months. Weakness distribution is primarily proximal in dermatomyositis and polymyositis, but distal muscles may become involved as the disease progresses. In contrast, distal muscle weakness is often the initial presentation in inclusion body myositis. Polymyositis onset is usually after the second decade of life. Dermatomyositis has two peak onsets: one around 10–15 years of age and another between 40 and 70 years. Inclusion body myositis typically occurs after age 50. Table 9.9 summarizes the pathogenetic mechanisms and clinical features of the most common IIM.
Table 9.9: Pathogenetic mechanisms and clinical features of common idiopathic inflammatory myopathies (IIMs), including dermatomyositis, polymyositis, and inclusion body myositis.
Dermatomyositis is characterized by distinctive cutaneous manifestations. Rashes may precede, follow, or occur concurrently with myopathy. Gottron’s papules and heliotrope rash are pathognomonic (specifically diagnostic) features of dermatomyositis [14]. Dermatomyositis and polymyositis can also cause cardiovascular, respiratory, and gastrointestinal manifestations.
Patients diagnosed with IIM have an increased risk of developing malignancies. Dermatomyositis and polymyositis are associated with a higher risk of malignancy, with dermatomyositis patients being three to six times more likely and polymyositis patients two to four times more likely than the general population to develop cancers such as ovarian, gastric, pancreatic, and lung cancer, as well as non-Hodgkin lymphoma. Therefore, malignancy screening is highly recommended in these patients [15].
Myopathy Due to Infectious Disease
Infectious diseases can cause acute weakness accompanied by muscle cramps, myoglobinuria (myoglobin in urine), and rhabdomyolysis. Viral infections are the most common infectious cause. Myalgia is the predominant symptom, which can last for 2–3 weeks. Myopathy due to viral infections is usually self-limiting, but severe cases can lead to myoglobinuria and kidney impairment.
Human immunodeficiency virus (HIV) infection is an important consideration in the differential diagnosis of myopathy, often referred to as HIV polymyositis. HIV polymyositis can be an initial manifestation of HIV infection or occur in later stages. Patients may present with asymptomatic elevation of CK levels or with severe muscle tenderness and weakness. HIV-related myopathy generally has a better prognosis than idiopathic inflammatory myopathies.
Diagnostic Approach
A thorough history and physical examination are the cornerstones of reaching an accurate diagnosis. Investigations should be tailored to screen for reversible causes of myopathy (Figure 9.4).
Fig. 9.4: Diagnostic approach flowchart for statin-induced myopathy, guiding evaluation and management strategies for patients on statin therapy.
When the cause of muscle weakness is unclear, appropriate blood tests should be performed, starting with electrolytes (potassium, calcium, phosphate, and magnesium), thyroid-stimulating hormone (TSH) level, alkaline phosphatase and 25-hydroxy vitamin D level, and HIV testing [16].
Muscle Enzymes
Measuring serum levels of muscle enzymes is crucial for evaluating and monitoring muscular disorders. Creatine kinase (CK), lactate dehydrogenase (LD), alanine aminotransferase (ALT), aspartate aminotransferase (AST), and aldolase are commonly measured muscle enzymes in clinical practice. In patients with suspected myopathy who do not show CK elevation, testing for aldolase can be helpful, though it is less sensitive and specific than CK [17].
Table 9.10 outlines the approach to elevated CK levels. It’s important to note that CK elevation is not specific to myopathy, and further comprehensive testing is necessary. Table 9.11 presents the differential diagnosis for elevated CK levels.
Table 9.10: Diagnostic approach to elevated creatine kinase (CK) levels, guiding further investigations based on CK level and clinical context.
Table 9.11: Differential diagnosis for elevated creatine kinase (CK) levels, encompassing muscular and non-muscular conditions that can cause CK elevation.
In diagnosing myocardial infarction (heart attack), along with symptoms and ECG abnormalities, CK-MB, the cardiac-specific isoenzyme of CK, will be elevated. However, troponins are now considered more specific and sensitive markers for cardiac muscle damage [18].
CK levels can be falsely elevated due to factors such as ethnicity (higher in Afro-Caribbean men), exercise (elevation can last up to 72 hours), intramuscular injections, needle electromyography (EMG), certain medications, hypothyroidism, and motor neuron disease [16].
Rhabdomyolysis
Rhabdomyolysis, or muscle breakdown, can be caused by strenuous exercise, medications, infections, and metabolic disturbances. Typical initial symptoms include severe myalgia, weakness, and red to brown urine due to myoglobinuria. CK levels typically rise within 2–12 hours of muscle injury, peaking at 24–72 hours, and usually decline within 3–5 days after cessation of muscle injury. Myoglobinuria is present in 50–75% of patients at initial evaluation. Routine urine dipstick analysis is recommended for patients with extremely elevated CK levels and myopathy. Rhabdomyolysis can lead to serious metabolic derangements, including electrolyte imbalances and acute renal failure.
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 cases of suspected inflammatory myopathy, testing for anti-Jo1 antibody, directed against histidyl-tRNA synthetase, is important. Anti-Jo1 syndrome is associated with extra-muscular features such as interstitial lung disease, Raynaud’s phenomenon, and arthritis [19].
Electromyography (EMG)
Electromyography (EMG) is a diagnostic test that records muscle electrical activity and assesses the nerves controlling muscles. Abnormal EMG results can indicate neuropathy or neuromuscular disease. EMG findings characteristic of myopathy include short duration and decreased amplitude of action potentials, unlike neuropathies which typically show increased duration and amplitude. While EMG findings are not pathognomonic for specific types of myopathy, EMG can help differentiate inflammatory from non-inflammatory myopathies. However, a normal EMG does not exclude myopathy [18]. In cases of suspected polymyositis, the muscle biopsy site should be contralateral to the EMG site [16].
Muscle Magnetic Resonance Imaging (MRI)
Muscle MRI evaluates deep muscles not easily accessible by EMG and aids in diagnosis by identifying subclinical muscle involvement. Fat-suppressed and short tau inversion recovery (STIR) techniques can differentiate between active myositis, visualized as edema, and chronic inactive myositis in inflammatory myopathy patients, seen as fat deposition [20]. Muscle MRI can also guide muscle biopsy site selection by identifying muscles most affected by the myopathic process.
Muscle Biopsy
Histopathological examination of muscle tissue is essential for establishing the diagnosis of idiopathic inflammatory myopathies (IIM). Advanced therapies are available for IIM, and muscle biopsy provides crucial justification for using these treatments, including steroids. Open surgical biopsy is generally preferred over closed needle biopsy due to the patchy nature of inflammation in polymyositis and to ensure adequate tissue sample collection. However, in certain situations, biopsies may be performed by experienced radiologists. Muscle biopsy is a reliable diagnostic tool in approximately 85% of patients with polymyositis [18]. It is typically an outpatient procedure, but potential complications include pain, bleeding, infection, or sensory loss. Patients should discontinue anticoagulant medications prior to the procedure [21].
The optimal muscles for biopsy are those moderately affected by the disease but not severely atrophied. Sites of previous injections, EMG examination, or trauma should be avoided. Common biopsy sites for proximal myopathy include the deltoid and quadriceps muscles, while the gastrocnemius muscle is often used for distal myopathies.
Genetic marker technology is rapidly advancing. In inflammatory myopathies, immune staining for major histocompatibility classes I and II (MHC-I/II) is upregulated in myofibrils. MHC-I immune staining alone is less specific [22].
Screening for Malignancy
Idiopathic inflammatory myopathies, particularly polymyositis and dermatomyositis, have a known association with malignancy. Retrospective studies support the use of CT scans of the chest, abdomen, and pelvis, along with age-appropriate screening tests like colonoscopy and mammography, for newly diagnosed patients. In Southeast Asia, otolaryngologist input is particularly valuable due to the higher incidence of nasopharyngeal carcinoma in dermatomyositis patients. Recent advances in understanding IIM pathogenesis have led to the discovery of biomarkers, such as type 1 interferon and myeloid cell signatures, which may help differentiate active disease from chronic injury [17].
Genetic Testing
Genetic testing is increasingly useful in confirming diagnoses of muscular dystrophies and heritable myopathies. Gene mutations can be identified through peripheral blood DNA analysis, often eliminating the need for muscle biopsy.
Management of Myopathy
Inherited Myopathy
For most patients with congenital myopathy or muscular dystrophy, treatment is primarily supportive. Physical therapy, occupational therapy, management of contractures, nutritional support, and genetic counseling are important components of care. In Duchenne muscular dystrophy, prednisone treatment has been shown to improve muscle strength and bulk and slow disease progression. Patients should be monitored for complications such as kyphoscoliosis and cardiac, respiratory, or bulbar muscle involvement. Genetic counseling should be offered to patients with inherited myopathies and their families.
Acquired Myopathy
Management of proximal myopathy depends on the underlying cause. Treatable causes should be identified and addressed. Discontinuation of the offending drug is usually effective for drug-induced myopathies, such as statin-induced myopathy [5]. Dose reduction should be considered when abrupt drug discontinuation is not feasible, such as in steroid myopathy [6]. In HIV-related myositis, treatment with highly active antiretroviral therapy (HAART) combined with steroids may be beneficial.
Treatment of idiopathic inflammatory myopathies (IIM) is largely empirical due to limited well-controlled clinical trials. Current evidence is mainly based on retrospective or open prospective trials with small patient numbers. Corticosteroids are the cornerstone of treatment for polymyositis and dermatomyositis [19, 20]. While optimal initial dose and treatment duration are uncertain due to lack of placebo-controlled trials, a common starting dose is 0.75–1 mg/kg body weight/day of prednisolone. Intravenous pulse methylprednisolone may be considered initially for patients with cardiac, respiratory, or pharyngeal muscle involvement to achieve a quicker response. Prednisolone dose tapering is typically initiated after 4–12 weeks, guided by clinical improvement, as maximal improvement may take several weeks. Many patients experience relapses upon corticosteroid discontinuation, often requiring a maintenance dose of 5–10 mg/day for several years. Approximately one-third of patients with polymyositis, dermatomyositis, or IIM may not respond to prednisolone alone. Second-line immunosuppressive drugs, such as azathioprine [23] or methotrexate, are used for patients who do not respond to corticosteroids or have progressive disease or internal organ involvement. Intravenous immunoglobulin (IVIg), for which randomized placebo-controlled trial evidence exists [21, 24], is particularly useful for dysphagia and treatment-resistant dermatomyositis, though it is expensive and has limited availability. Cyclophosphamide, administered as monthly intravenous pulses for 3–6 months, is an option for respiratory muscle weakness, interstitial lung disease, or cardiac involvement [25]. Plasmapheresis has been studied but was not found helpful in a double-blind placebo-controlled trial [26]. Rituximab, a CD20 monoclonal antibody that depletes B cells, has shown favorable effects in small open-label trials [27, 28]. A recent double-blind, placebo-controlled trial of rituximab in refractory adult and pediatric myositis showed promising results [29]. Tumor necrosis factor (TNF) inhibitors like infliximab, adalimumab, and etanercept are ineffective and may worsen or trigger IIM [30, 31]. Other experimental biological agents include alemtuzumab, reported to be effective in polymyositis [31], and anti-complement C3 (eculizumab), potentially effective for dermatomyositis. Overall, the long-term outcome for inflammatory myopathies has improved substantially, with a 10-year survival rate exceeding 90%. Table 9.12 outlines a step-by-step approach to managing IIM [32].
Table 9.12: Step-by-step approach to the treatment of inflammatory myopathies, outlining therapeutic strategies based on disease severity and response to initial treatments.
Physiotherapy is also valuable, as randomized controlled trials in IIM patients have demonstrated that exercise therapy, tailored to the patient’s condition, is safe and beneficial [33]. Exercise benefits include improved muscle endurance, strength, and functional abilities, as well as prevention of muscle wasting and fibrotic contractures.
Acknowledgments
The authors acknowledge Haytham Abbas, MD, for his contributions to this chapter in the previous edition.
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