on 30-Jun-2021 (Wed)

Excessive exertion, trauma, and viral infections are among the most common causes

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

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

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.

Rheumatic disease, especially polymyalgia rheumatica (PMR), inflammatory myopathy [9,10], or autoinflammatory disease [11].

Particular attention should be given to mode of onset, location of pain, and associated symptoms.

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 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, headache, malaise, and a nonproductive cough are typical of a viral infection, such as influenza.

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.

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.

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.

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 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.

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.

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 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 infection. Severe, localized tenderness without inflammatory features suggests muscle infarction or compartment syndrome.

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.