Myalgia

Muscle pain is a common finding in muscle disease, and some myopathies are associated with rhabdomyolysis. A VINDICATE-style differential helps structure the approach to generalised or widespread muscle pain.

Differential diagnosis

Category	Causes
Vascular	Polyarteritis nodosa
Infectious	Viral infections (very common — influenza, COVID-19, EBV, enteroviruses); bacterial and fungal myositis
Neoplasia	Leiomyoma, rhabdomyoma, rhabdosarcoma; paraneoplastic syndromes
Degenerative	Osteoarthritis-associated muscle pain
Iatrogenic/intoxication	Statins (most common drug cause), corticosteroids, colchicine, hydroxychloroquine, amiodarone, alcohol, checkpoint inhibitors
Congenital	Duchenne muscular dystrophy, spinal muscular atrophy
Autoimmune	Fibromyalgia, polymyalgia rheumatica, polymyositis/dermatomyositis
Trauma	Post-exercise (delayed-onset muscle soreness), rhabdomyolysis, crush injury
Endocrine/metabolic	Hypothyroidism, hyperthyroidism, hyperparathyroidism, Addison’s, Cushing’s, electrolyte disturbance, vitamin D deficiency

Clinical approach

Distinguish myalgia from true muscle weakness. Ask specifically about difficulty rising from a chair, climbing stairs or reaching overhead. Myopathy typically presents as proximal weakness in the pelvic or shoulder girdle, with the pelvic group more commonly and more severely affected — that pattern points towards an inflammatory myopathy or polymyalgia rheumatica rather than a self-limiting pain syndrome.

Myopathy is a motor problem: sensory symptoms should be absent. Their presence suggests a neuropathic cause instead.

Endocrine myopathy is worth remembering because it is treatable. Both hypo- and hyperthyroid disease cause proximal weakness with peripheral neuropathy; hypothyroid myopathy adds pseudohypertrophy, myoedema and delayed reflexes, while hyperthyroid myopathy comes with goitre, ophthalmopathy and extraocular weakness.

Red flags warranting urgent work-up

• Dark, reddish or tea-coloured urine — myoglobinuria
• Marked CK elevation
• Rapidly progressive weakness
• Systemic features such as fever or weight loss

These point to rhabdomyolysis, an inflammatory myopathy, or a vasculitic process.

Investigations

CK is the most useful blood test, but the level may not correlate with the degree of weakness, and some myopathies present with a normal CK and a selectively raised aldolase. Add CRP and ESR, thyroid function, electrolytes including calcium and phosphate, and vitamin D.

Rhabdomyolysis

Skeletal muscle breaks down and releases myoglobin, creatine phosphokinase, electrolytes and sarcoplasmic proteins into the bloodstream, risking acute kidney injury, electrolyte disturbance and DIC. Typical symptoms are myalgia, weakness, dark urine and local swelling, with CK often above five times the upper limit of normal.

Common causes are crush injury, prolonged immobilisation, strenuous exertion, alcohol and drug toxicity, viral illness, sepsis and inherited myopathies. Early hydration is the priority — the goal of treatment is preventing acute kidney injury with aggressive IV fluids and close monitoring of renal function and electrolytes.

Statin-associated muscle symptoms

Myopathy is one of the commonest statin adverse effects, is dose-dependent, and may present as diffuse myalgia or unexplained muscle tenderness or weakness that reverses on stopping the drug. About 0.5% of patients taking statins develop clinically significant myonecrosis.

Symptoms usually improve or resolve when the dose is reduced or the drug stopped, so try a dose reduction, an alternate-day regimen, or a switch to a different statin. Diagnosing true statin intolerance requires trialling at least two statins. Routine CK monitoring is not required unless the patient is symptomatic.

Watch the interactions that raise statin levels and myopathy risk — CYP3A4 inhibitors with atorvastatin, lovastatin or simvastatin, and fibrates (simvastatin plus gemfibrozil is contraindicated). Monitor creatine kinase when colchicine is co-prescribed with a statin.

Statin-associated immune-mediated necrotising myopathy is a distinct entity caused by antibodies against HMG-CoA reductase: symmetrical proximal weakness with markedly raised CK that persists for months after the statin is stopped, and it needs immunosuppression rather than simple drug withdrawal.

Fibromyalgia

Widespread pain with normal examination and investigations, especially with fatigue, sleep disturbance and cognitive symptoms, points towards fibromyalgia — see musculoskeletal/fibromyalgia for the full approach.