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Excessive exertion, trauma, and viral infections are among the most common causes
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20. INTRODUCTION — Myalgia, or muscle pain, is a common complaint among adults presenting for medical care. In fact, nearly everyone will experience muscle soreness at some point in their life. <span>Excessive exertion, trauma, and viral infections are among the most common causes. While many causes are benign and self-limited, myalgia may be the harbinger of disorders associated with significant morbidity. A thorough review of the patient's history and a complet




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It is important to differentiate myalgia from myopathy (muscle disease) and myositis (muscle inflammation). Although myopathy and myositis may cause myalgia, most individuals with myalgia have neither. It is also useful to separate diffuse from localized symptoms
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uses of myalgia to a manageable few. For persistent or severe myalgia without a known cause, selected testing may be necessary to identify or exclude specific diagnoses and to direct treatment. <span>It is important to differentiate myalgia from myopathy (muscle disease) and myositis (muscle inflammation). Although myopathy and myositis may cause myalgia, most individuals with myalgia have neither. It is also useful to separate diffuse from localized symptoms. This review will discuss the approach to myalgia as a presenting symptom to a primary care clinician, focusing on etiology, history, physical examination, laboratory studies, and manag




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Metabolic disorders, such as mitochondrial myopathy [20,21], vitamin D deficiency [22,23], and scurvy [24], can lead to myalgias, although these are rarer causes
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out creatine kinase elevation) [13,14], ciprofloxacin [15], bisphosphonates [16], aromatase inhibitors [17,18], or withdrawal from antidepressant therapy [19]. (See "Drug-induced myopathies".) ●<span>Metabolic disorders, such as mitochondrial myopathy [20,21], vitamin D deficiency [22,23], and scurvy [24], can lead to myalgias, although these are rarer causes. (See "Approach to the metabolic myopathies" and "Mitochondrial myopathies: Clinical features and diagnosis".) ●Liver disease, such as chronic viral hepatitis and autoimmune hepatitis [




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Endocrine disorders, such as thyroid disease [26,27] and adrenal insufficiency [28] can lead to myopathic pain. Of note, glucocorticoid-induced myopathy often leads to muscle weakness and wasting without pain.
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(See "Approach to the metabolic myopathies" and "Mitochondrial myopathies: Clinical features and diagnosis".) ●Liver disease, such as chronic viral hepatitis and autoimmune hepatitis [2,3,25]. ●<span>Endocrine disorders, such as thyroid disease [26,27] and adrenal insufficiency [28] can lead to myopathic pain. Of note, glucocorticoid-induced myopathy often leads to muscle weakness and wasting without pain. (See "Hypothyroid myopathy" and "Glucocorticoid-induced myopathy".) ●Psychiatric, as with somatic manifestations of depression [29,30]. Localized myalgia — The most common causes of loc




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Rheumatic disease, especially polymyalgia rheumatica (PMR), inflammatory myopathy [9,10], or autoinflammatory disease [11].
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rus. Prominent myalgia is also a typical feature of influenza [7] and coronavirus disease 2019 (COVID-19) [8]. In addition, vaccination may also cause significant, though short-lived, myalgia. ●<span>Rheumatic disease, especially polymyalgia rheumatica (PMR), inflammatory myopathy [9,10], or autoinflammatory disease [11]. (See "Clinical manifestations and diagnosis of polymyalgia rheumatica" and "Clinical manifestations of dermatomyositis and polymyositis in adults".) ●Noninflammatory conditions, such as




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Particular attention should be given to mode of onset, location of pain, and associated symptoms.
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myolysis" and "Acute compartment syndrome of the extremities".) History — The patient's history provides a useful starting point in narrowing down the long list of potential causes for myalgia. <span>Particular attention should be given to mode of onset, location of pain, and associated symptoms. Muscle symptoms — The first step in determining the cause of myalgia is to inquire about the specific nature of the patient's muscle pain: ●Did the muscle pain begin suddenly or gradual




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Did the muscle pain begin suddenly or gradually? If sudden in onset, did it follow trauma or an unusually strenuous activity? Is the muscle pain worse in the morning?

As an example, acute onset with prominent constitutional symptoms suggests infection (such as bacterial sepsis, pyomyositis, influenza or acute hepatitis B). Acute onset of myalgia in the neck, shoulders, upper arms, buttocks, and thighs in an older adult is characteristic of polymyalgia rheumatica (PMR), especially if accompanied by morning stiffness.

Subacute myalgia is typical of a medication-induced cause (such as statin-induced myalgia) and can occur weeks to months after initiating therapy. (See "Statin muscle-related adverse events", section on 'Management'.)

Insidious onset and chronic symptoms are typical of infection with chronic hepatitis C, hypothyroidism, hypercalcemia, and vitamin D deficiency. This is also the typical pattern for patients with fibromyalgia, chronic fatigue syndrome (CFS), myofascial pain syndrome, and a somatization disorder.

In addition, muscle pain and stiffness in the morning is highly suggestive of PMR or other inflammatory arthritis.

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of onset, location of pain, and associated symptoms. Muscle symptoms — The first step in determining the cause of myalgia is to inquire about the specific nature of the patient's muscle pain: ●<span>Did the muscle pain begin suddenly or gradually? If sudden in onset, did it follow trauma or an unusually strenuous activity? Is the muscle pain worse in the morning? As an example, acute onset with prominent constitutional symptoms suggests infection (such as bacterial sepsis, pyomyositis, influenza or acute hepatitis B). Acute onset of myalgia in the neck, shoulders, upper arms, buttocks, and thighs in an older adult is characteristic of polymyalgia rheumatica (PMR), especially if accompanied by morning stiffness. Subacute myalgia is typical of a medication-induced cause (such as statin-induced myalgia) and can occur weeks to months after initiating therapy. (See "Statin muscle-related adverse events", section on 'Management'.) Insidious onset and chronic symptoms are typical of infection with chronic hepatitis C, hypothyroidism, hypercalcemia, and vitamin D deficiency. This is also the typical pattern for patients with fibromyalgia, chronic fatigue syndrome (CFS), myofascial pain syndrome, and a somatization disorder. In addition, muscle pain and stiffness in the morning is highly suggestive of PMR or other inflammatory arthritis. ●Is the muscle pain associated with pain elsewhere? Is it near joints? If so, are they axial joints, such as the shoulder and hips? Shoulder and hip pathology, in particular, tend to ca




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Is the muscle pain associated with pain elsewhere? Is it near joints? If so, are they axial joints, such as the shoulder and hips? Shoulder and hip pathology, in particular, tend to cause referred pain to proximal muscles. Referred pain accounts for the prominent myalgia described by patients with PMR and rheumatoid arthritis involving the shoulders.
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atigue syndrome (CFS), myofascial pain syndrome, and a somatization disorder. In addition, muscle pain and stiffness in the morning is highly suggestive of PMR or other inflammatory arthritis. ●<span>Is the muscle pain associated with pain elsewhere? Is it near joints? If so, are they axial joints, such as the shoulder and hips? Shoulder and hip pathology, in particular, tend to cause referred pain to proximal muscles. Referred pain accounts for the prominent myalgia described by patients with PMR and rheumatoid arthritis involving the shoulders. ●Is there a particular distribution of muscle pain? Statin-induced myalgia typically presents as proximal, symmetric muscle weakness and soreness. By contrast, diffuse myalgia, fever, h




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Is there a particular distribution of muscle pain? Statin-induced myalgia typically presents as proximal, symmetric muscle weakness and soreness. By contrast, diffuse myalgia, fever, headache, malaise, and a nonproductive cough are typical of a viral infection, such as influenza.
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n particular, tend to cause referred pain to proximal muscles. Referred pain accounts for the prominent myalgia described by patients with PMR and rheumatoid arthritis involving the shoulders. ●<span>Is there a particular distribution of muscle pain? Statin-induced myalgia typically presents as proximal, symmetric muscle weakness and soreness. By contrast, diffuse myalgia, fever, headache, malaise, and a nonproductive cough are typical of a viral infection, such as influenza. (See "Statin muscle-related adverse events" and "Seasonal influenza in adults: Transmission, clinical manifestations, and complications".) ●Is there redness, swelling, or warmth in the




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Is the myalgia associated with muscle weakness? Is it difficult to arise from a chair or reach above the head? Objective muscle weakness is not expected with fibromyalgia, myofascial pain syndrome, or PMR; these common causes of muscle pain can be placed lower on the list of possibilities in the face of demonstrable muscle weakness.
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painful to touch? Pyomyositis, abscess, muscle infarction, or compartment syndrome may cause focal muscle tenderness. Pyomyositis and abscess may cause localized inflammatory findings as well. ●<span>Is the myalgia associated with muscle weakness? Is it difficult to arise from a chair or reach above the head? Objective muscle weakness is not expected with fibromyalgia, myofascial pain syndrome, or PMR; these common causes of muscle pain can be placed lower on the list of possibilities in the face of demonstrable muscle weakness. (See "Approach to the patient with muscle weakness".) ●Have there been muscle cramps? The etiology of muscle cramps is often not found, but they can be caused by several conditions: •St




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Is there redness, swelling, or warmth in the area of the muscle pain? Is the muscle painful to touch? Pyomyositis, abscess, muscle infarction, or compartment syndrome may cause focal muscle tenderness. Pyomyositis and abscess may cause localized inflammatory findings as well.
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are typical of a viral infection, such as influenza. (See "Statin muscle-related adverse events" and "Seasonal influenza in adults: Transmission, clinical manifestations, and complications".) ●<span>Is there redness, swelling, or warmth in the area of the muscle pain? Is the muscle painful to touch? Pyomyositis, abscess, muscle infarction, or compartment syndrome may cause focal muscle tenderness. Pyomyositis and abscess may cause localized inflammatory findings as well. ●Is the myalgia associated with muscle weakness? Is it difficult to arise from a chair or reach above the head? Objective muscle weakness is not expected with fibromyalgia, myofascial p




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Have there been muscle cramps? The etiology of muscle cramps is often not found, but they can be caused by several conditions:

• Structural disorders such as flat feet

• Unusual positioning during work or sleep

• Neurologic disorders such as Parkinson disease

• Muscle injury such as trauma or fall

• Dehydration

• Exercise-associated muscle cramping or spasm

• Electrolyte abnormalities

• Medications such as diuretics, statins, and beta agonists.

Leg cramps occurring at night are discussed separately.

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, or PMR; these common causes of muscle pain can be placed lower on the list of possibilities in the face of demonstrable muscle weakness. (See "Approach to the patient with muscle weakness".) ●<span>Have there been muscle cramps? The etiology of muscle cramps is often not found, but they can be caused by several conditions: •Structural disorders such as flat feet •Unusual positioning during work or sleep •Neurologic disorders such as Parkinson disease •Muscle injury such as trauma or fall •Dehydration •Exercise-associated muscle cramping or spasm •Electrolyte abnormalities •Medications such as diuretics, statins, and beta agonists. Leg cramps occurring at night are discussed separately. (See "Nocturnal leg cramps".) Associated symptoms — The presence or absence of associated symptoms can be quite helpful in pointing toward or against a particular cause. The clinician s




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The clinician should undertake a detailed review of systems with particular attention paid to:

● Constipation

● Depression

● Fatigue

● Fever

● Joint pain or swelling

● Paresthesias

● Rash or hyperpigmentation

● Weight change

● Nausea, vomiting or diarrhea

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e discussed separately. (See "Nocturnal leg cramps".) Associated symptoms — The presence or absence of associated symptoms can be quite helpful in pointing toward or against a particular cause. <span>The clinician should undertake a detailed review of systems with particular attention paid to: ●Constipation ●Depression ●Fatigue ●Fever ●Joint pain or swelling ●Paresthesias ●Rash or hyperpigmentation ●Weight change ●Nausea, vomiting or diarrhea Constipation, fatigue, and weight gain are common symptoms of hypothyroidism, whereas rash or hyperpigmentation are suggestive of infection or adrenal insufficiency, respectively. Fever




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Constipation, fatigue, and weight gain are common symptoms of hypothyroidism, whereas rash or hyperpigmentation are suggestive of infection or adrenal insufficiency, respectively. Fever raises the possibility of infection or systemic rheumatic disease (such as systemic lupus erythematosus) or autoinflammatory disease (such as familial Mediterranean fever) while joint swelling suggests inflammatory arthritis. Paresthesias suggest a neuropathic condition, which may cause myalgia due to referred pain or indicate the presence of a vasculitic process.
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ystems with particular attention paid to: ●Constipation ●Depression ●Fatigue ●Fever ●Joint pain or swelling ●Paresthesias ●Rash or hyperpigmentation ●Weight change ●Nausea, vomiting or diarrhea <span>Constipation, fatigue, and weight gain are common symptoms of hypothyroidism, whereas rash or hyperpigmentation are suggestive of infection or adrenal insufficiency, respectively. Fever raises the possibility of infection or systemic rheumatic disease (such as systemic lupus erythematosus) or autoinflammatory disease (such as familial Mediterranean fever) while joint swelling suggests inflammatory arthritis. Paresthesias suggest a neuropathic condition, which may cause myalgia due to referred pain or indicate the presence of a vasculitic process. Other history — The cause of myalgia may not be apparent until additional details of the patient's medical history are revealed. These include: ●Patient demographics, such as age and ge




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Medication use, especially statin administration, can lead to myalgias.

Myalgia due to statin or fibrate medications may be associated with weakness and an elevation in creatine kinase, but these features are often absent [36]. Drug interactions account for many cases of medication-induced myalgia or myopathy, particularly in patients taking statins and inhibitors of CYP3A4 (table 3). A number of other common medications may be associated with myalgia, including bisphosphonates and aromatase inhibitors.

In addition, abrupt discontinuation of serotonin-reuptake inhibitors with short half-lives (such as venlafaxine or paroxetine) may cause significant myalgia [29,30]. Muscle symptoms that follow the administration of a new medication should prompt the clinician to consider drug-induced muscle pain.

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adult women, while PMR is seen exclusively among adults over the age of 55. ●Past medical history, such as a prior diagnosis of thyroid disease, hepatitis C, diabetes, or hyperparathyroidism. ●<span>Medication use, especially statin administration, can lead to myalgias. Myalgia due to statin or fibrate medications may be associated with weakness and an elevation in creatine kinase, but these features are often absent [36]. Drug interactions account for many cases of medication-induced myalgia or myopathy, particularly in patients taking statins and inhibitors of CYP3A4 (table 3). A number of other common medications may be associated with myalgia, including bisphosphonates and aromatase inhibitors. In addition, abrupt discontinuation of serotonin-reuptake inhibitors with short half-lives (such as venlafaxine or paroxetine) may cause significant myalgia [29,30]. Muscle symptoms that follow the administration of a new medication should prompt the clinician to consider drug-induced muscle pain. (See "Statin muscle-related adverse events" and "Drug-induced myopathies".) ●Trauma, a change in activity or function, recent injury, or unusually strenuous exercise may trigger muscle




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For example, the finding of proximal muscle weakness in all four extremities in a patient with myalgia should turn the focus of diagnostic considerations to inflammatory myopathy (such as polymyositis), hypothyroidism, drug-induced myopathy, or hypercalcemia. Identifying objective weakness is important because weakness (with or without myalgia) is a common complaint even in the absence of demonstrable loss of motor function.
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tient with myalgia to cooperate fully with a muscle examination, the finding of weakness can be particularly helpful in narrowing down the list of possible causes of symptoms by excluding many. <span>For example, the finding of proximal muscle weakness in all four extremities in a patient with myalgia should turn the focus of diagnostic considerations to inflammatory myopathy (such as polymyositis), hypothyroidism, drug-induced myopathy, or hypercalcemia. Identifying objective weakness is important because weakness (with or without myalgia) is a common complaint even in the absence of demonstrable loss of motor function. Even patients with significant pain can usually give maximum effort at least briefly to provide the examiner with a sense of whether muscle strength is normal. Besides assessing muscle




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Even patients with significant pain can usually give maximum effort at least briefly to provide the examiner with a sense of whether muscle strength is normal. Besides assessing muscle strength in the usual proximal and distal muscle groups (including deltoids, wrist extensors, grip, thigh flexors, and ankle flexors and extensors), assessment of neck flexor strength may be useful as these muscles are a powerful and often overlooked proximal muscle group.
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pathy, or hypercalcemia. Identifying objective weakness is important because weakness (with or without myalgia) is a common complaint even in the absence of demonstrable loss of motor function. <span>Even patients with significant pain can usually give maximum effort at least briefly to provide the examiner with a sense of whether muscle strength is normal. Besides assessing muscle strength in the usual proximal and distal muscle groups (including deltoids, wrist extensors, grip, thigh flexors, and ankle flexors and extensors), assessment of neck flexor strength may be useful as these muscles are a powerful and often overlooked proximal muscle group. Besides the assessment of weakness, helpful findings on muscle examination may include focal swelling or erythema, which should raise the possibility of pyomyositis or other localized i




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Besides the assessment of weakness, helpful findings on muscle examination may include focal swelling or erythema, which should raise the possibility of pyomyositis or other localized infection. Severe, localized tenderness without inflammatory features suggests muscle infarction or compartment syndrome.
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st extensors, grip, thigh flexors, and ankle flexors and extensors), assessment of neck flexor strength may be useful as these muscles are a powerful and often overlooked proximal muscle group. <span>Besides the assessment of weakness, helpful findings on muscle examination may include focal swelling or erythema, which should raise the possibility of pyomyositis or other localized infection. Severe, localized tenderness without inflammatory features suggests muscle infarction or compartment syndrome. (See "Diabetic muscle infarction" and "Acute compartment syndrome of the extremities".) It should be noted that muscle weakness without pain includes a much broader differential diagnos




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As an initial assessment, complete blood count, urinalysis, and measures of renal and liver function are appropriate for most patients with significant myalgia. Depending upon the specific symptoms, risk factors and physical findings, measures of serum calcium, albumin, phosphate, TSH, creatine kinase, and 25-hydroxyvitamin D may be appropriate to assess, especially if symptoms are prominent, persistent, and otherwise unexplained. Weakness should prompt creatine kinase measurement while bone pain and/or abnormal measures of serum calcium make it important to test for hypovitaminosis D. Cold intolerance, fatigue, and delayed reflexes may suggest hypothyroidism as a cause of myalgia.
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le weakness), selected laboratory studies may be quite helpful in ruling in or ruling out conditions that remain in the differential diagnosis after a detailed history and physical examination. <span>As an initial assessment, complete blood count, urinalysis, and measures of renal and liver function are appropriate for most patients with significant myalgia. Depending upon the specific symptoms, risk factors and physical findings, measures of serum calcium, albumin, phosphate, TSH, creatine kinase, and 25-hydroxyvitamin D may be appropriate to assess, especially if symptoms are prominent, persistent, and otherwise unexplained. Weakness should prompt creatine kinase measurement while bone pain and/or abnormal measures of serum calcium make it important to test for hypovitaminosis D. Cold intolerance, fatigue, and delayed reflexes may suggest hypothyroidism as a cause of myalgia. The following tests may also prove helpful in certain clinical situations (table 1): ●Blood cultures and serologic testing for infectious agents (such as parvovirus and viral hepatitis)