Investigating myalgia – a rational testing approach

Rational testing: In the first of our new series on how to rationalise testing in primary care, chemical pathologist Dr Kate Shipman explains the most logical approach to investigating a case of myalgia in order to rule out serious pathology and reach a diagnosis

Note cases in this series are hypothetical scenarios developed for illustrative purposes

Case:  A 32-year-old female patient presents with muscle ‘aches and pains’ she has suffered for a year or so. She has seen a number of your primary care colleagues and says that, after an internet search, she has landed on the idea that she might have fibromyalgia. She has had some blood tests. There are no features of any inflammatory joint disease, no unusual rashes and her symptoms do sound compatible with fibromyalgia. You want to rule out other potential mimics.

What are potential causes of subacute or chronic myalgia?

Fibromyalgia is a diagnosis of exclusion. However, injudicious use of investigations can result in false positives that will only serve to complicate the situation.

The most common possible causes in the case described would be:  

• Fibromyalgia.
• Connective tissue disease.
• Hypothyroidism.
• Medication side effect (statins).
• Osteomalacia.
• Chronic fatigue syndrome.
• Neuropathy.
• Myositis.
• Polymyalgia rheumatica (in older patients).

Features in the history and examination can help to narrow down potential underlying conditions.

A more detailed consideration of potential causes is provided in Table 1.

Table 1: Potential causes of subacute/chronic myalgia and associated features

What are the basic minimum, first-line tests to consider?

Basic and cost-effective tests include:

• Full blood count (FBC).
• Renal, liver and thyroid function.
• Creatinine kinase (CK).
• Inflammatory markers.

Consider also: calcium; magnesium; HbA1c; and phosphate.

Inflammatory conditions can raise C-reactive protein (CRP), erythrocyte sedimentation rate (ESR) or both. Therefore both tests may be indicated if considering autoimmune pathologies.

Elevated CK confirms that muscle is the source of symptoms. However, myopathy mimics may be excluded by screening for diabetes, neuropathy (and anaemia) and ischaemia (claudication). If ischaemia is suspected, a lipid profile should be done.

Osteomalacia, caused by vitamin D deficiency, is rare in the UK. However, as osteomalacia is an easily treatable cause of myalgia, consider screening in those with risk factors – for example, very little limited sunlight exposure and malnutrition. Note most vitamin D comes from endogenous synthesis via sunlight exposure therefore individuals with malabsorption have a low risk of hypovitaminosis D.

Malignancy and paraneoplastic syndromes are also possible causes to consider. Multiple myeloma mostly causes muscle pain secondary to bone and nerve pathology (CK and ALP usually normal but a high globulin is indicated by a raised ESR, in which case arrange serum electrophoresis).

What second-line laboratory tests might the GP consider?

In those with significant muscle wasting CK may not be elevated, despite myopathy. Elevation of aspartate aminotransferase (AST) and lactate dehydrogenase (LDH), both enzymes found in high concentration in muscle, may be helpful to confirm a myopathy. If myopathy is confirmed, then specialist testing will be required to determine the cause, including an extended myositis screen or similar.

Endocrinopathies can also present with muscle aches. Other features of cortisol excess and deficiency, such as central adiposity and facial plethora or pigmentation of mucous membranes and postural hypotension, should help indicate if you require a 24-hour urine cortisol or early morning serum cortisol measurement respectively. Acromegaly can also cause myalgia and weakness without compression neuropathy.

Heavy metal – such as lead and arsenic – poisoning can cause myalgia. In addition to occupational contact or deliberate poisoning, exposure can occur from medications sourced from other countries (including organophosphates), cosmetics and hair dyes, skin creams, eating paint and contaminated water.

Therefore a very in-depth and broad history may be required and discussion with poison units.

Carbon monoxide may also be associated with myalgia but will be indicated by other symptoms such as headache, dizziness and dyspnoea.

What tests should be avoided?

In patients with non-specific myalgia, do not undertake a connective tissue disease (CTD) screen for autoimmune diseases associated with presence of antinuclear antibodies (ANA), extractable nuclear antibodies (ENA) and double stranded DNA (dsDNA). This is only appropriate if there are other symptoms of systemic lupus erythematosus, systemic sclerosis or Sjogren’s, or you have a CK-positive myositis. Approximately 20-30% of the normal population have weakly positive ANA and conversely one can have seronegative autoimmune disease.

Similarly, rheumatoid factor (RhF) and/or cyclic citrullinated peptide (CCP) antibodies should be avoided in those with non-specific myalgia without a history or signs of rheumatoid arthritis.

Vitamin D should be avoided routinely as much of the UK population will have insufficiency/deficiency on testing but not have osteomalacia.

Zinc testing is also of no use. Though zinc supplements have been associated with improvements in conditions like fibromyalgia, myalgia is not a prominent symptom of true zinc deficiency (periorificial dermatitis is, however).

Likewise, although some people wear copper bands to combat symptoms of myalgia, copper measurement is not indicated.

Summary

Consider your testing strategy based on presentation and risk factors (see Table 2).

Although many conditions mentioned above are rare, even inborn errors of metabolism (other episodes of myalgia or rhabdomyolysis from childhood) can be first diagnosed in adulthood.

Therefore, it is likely that any GP will pick up at least one rare cause of myopathy in their clinical career; these are more likely if physical findings are present and there is a raised CK, atypical history or exposure to toxins/medications.

Table 2: Summary of laboratory investigation strategy for investigation of myalgia

*denotes tests that are more expensive than the routine biochemical tests (though there is significant difference in costs between those highlighted)

Dr Kate Shipman is a consultant chemical pathologist in West Sussex