What rheumatologic testing is recommended for a patient with rhabdomyolysis and suspected underlying rheumatologic condition?

Rheumatologic Testing in Rhabdomyolysis with Suspected Underlying Rheumatologic Condition

For patients with rhabdomyolysis and suspected underlying rheumatologic disease, obtain autoimmune markers including ANA, rheumatoid factor, anti-CCP antibodies, and myositis-specific antibodies, along with inflammatory markers (ESR and CRP), as these tests help differentiate immune-mediated myositis from other causes of rhabdomyolysis. 1, 2

Core Rheumatologic Laboratory Panel

When rhabdomyolysis occurs in the context of suspected autoimmune disease, the following tests are essential:

Autoimmune Markers

• Antinuclear antibody (ANA) should be checked to screen for systemic autoimmune conditions including lupus-like syndromes and inflammatory myositis 1, 2
• Rheumatoid factor (RF) and anti-cyclic citrullinated peptide (anti-CCP) antibodies help identify rheumatoid arthritis-like presentations, though these are typically negative in immune checkpoint inhibitor-associated arthritis 1
• Myositis-specific antibodies (including anti-TIF1γ, anti-NXP2, and other myositis autoantibodies) should be obtained, especially if muscle-related manifestations preceded any immunotherapy or if paraneoplastic myositis is suspected 1, 2
• Anti-smooth muscle antibody (ASMA) and anti-neutrophil cytoplasmic antibody (ANCA) should be considered if vasculitis or other autoimmune conditions are in the differential 2, 3

Inflammatory Markers

• Erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are essential to assess the degree of systemic inflammation and help distinguish inflammatory myositis from non-inflammatory causes 1, 2

Additional Specialized Testing Based on Clinical Context

Neuromuscular Evaluation

• Anti-acetylcholine receptor (anti-AChR) and antistriational antibodies should be obtained when overlap with myasthenia gravis is suspected, particularly if there is prominent weakness disproportionate to CK elevation 1
• Electromyography (EMG) should be considered when diagnosis is uncertain or when neurologic syndromes overlap with myositis, as it can show muscle fibrillations indicative of myopathy 1
• MRI imaging of affected muscles can demonstrate increased intensity and edema in inflammatory myositis, helping differentiate from other causes of rhabdomyolysis 1, 3

Cardiac Assessment in Myositis

• Troponin levels must be checked to evaluate for myocardial involvement, as myositis can affect the heart muscle and lead to life-threatening complications 1, 2
• ECG and echocardiogram or cardiac MRI should be performed if cardiac involvement is suspected based on troponin elevation or clinical symptoms 1

Critical Distinction: Myositis vs. Polymyalgia-Like Syndrome

A key clinical pitfall is distinguishing true inflammatory myositis from polymyalgia rheumatica-like syndromes:

• True myositis presents with weakness (not just pain) as the predominant symptom, with markedly elevated CK levels (often >5,000-10,000 IU/L), and EMG/MRI showing evidence of muscle inflammation 1, 2
• Polymyalgia-like syndrome presents with severe myalgia and fatigue but no true weakness, CK levels within normal limits, highly elevated inflammatory markers (ESR/CRP), and negative RF/anti-CCP 1

When to Obtain Muscle Biopsy

• Muscle biopsy should be performed on an individual basis when diagnosis remains uncertain after initial workup, when overlap syndromes are suspected, or when histology is needed to guide immunosuppressive therapy 1
• Biopsy is particularly useful when paraneoplastic autoantibody testing suggests specific myositis subtypes that may require targeted treatment 1

Timing and Urgency of Rheumatology Referral

• Urgent rheumatology referral is mandatory for Grade 3-4 myositis (severe weakness limiting self-care, rhabdomyolysis, respiratory or swallowing difficulties) 1
• Early rheumatology referral (Grade 2) is recommended when CK is elevated ≥3 times upper limit of normal with muscle weakness, as erosive joint damage can occur within weeks of symptom onset in inflammatory arthritis 1
• Even mild rheumatologic symptoms warrant referral if they persist beyond 6 weeks or require >20 mg prednisone daily that cannot be tapered below 10 mg/day within 4 weeks 1

Common Pitfalls to Avoid

• Do not rely solely on urine myoglobin testing, as qualitative dipstick/ultrafiltration is positive in only 19% of rhabdomyolysis cases despite confirmed muscle breakdown 4
• Do not assume negative RF and anti-CCP exclude inflammatory arthritis, as immune-mediated arthritis from checkpoint inhibitors or other causes is typically seronegative 1
• Do not delay testing for myositis-specific antibodies if there is any history of muscle symptoms before the acute rhabdomyolysis episode, as this suggests underlying paraneoplastic or autoimmune myopathy 1
• Do not overlook thyroid function testing, as hypothyroidism predisposes to statin-induced and other forms of drug-related rhabdomyolysis 2