Diagnostic Approach to Rapidly Progressive Selective Proximal Weakness

Immediate Diagnostic Priorities

The American College of Rheumatology suggests measuring respiratory function immediately with negative inspiratory force and vital capacity, as respiratory failure can develop insidiously before sudden decompensation in inflammatory myopathies 2
The European Neurological Society recommends obtaining urgent creatine kinase (CK) and aldolase levels - markedly elevated CK (often >10× normal) suggests IMNM, while moderate elevation (3-10× normal) suggests polymyositis or dermatomyositis 1, 2
Assess for bulbar symptoms including dysphagia, dysarthria, and facial weakness which indicate impending respiratory compromise 2
Check troponin and ECG to evaluate myocardial involvement, as cardiac manifestations can be life-threatening in inflammatory myopathies 2

Myositis-specific antibodies are essential: anti-SRP antibody indicates necrotizing myopathy with acute onset, dilated cardiomyopathy, and poor response to standard immunosuppression 3
Anti-Jo-1 and other anti-synthetase antibodies (anti-PL-7, anti-PL-12, anti-EJ, anti-OJ) - positive in 20-30% of inflammatory myositis cases 3
Anti-Mi2 antibody suggests dermatomyositis with classic cutaneous features 3
Urinalysis for myoglobinuria to assess for rhabdomyolysis 2

Immune-Mediated Necrotizing Myopathy (IMNM) is the top differential given the rapidly progressive course and selective pattern, with anti-SRP myopathy presenting with acute or subacute onset of severe proximal weakness, CK levels often exceeding 10 times normal, and minimal inflammatory infiltrate on biopsy 1, 3
Polymyositis/Dermatomyositis is characterized by symmetric proximal muscle weakness developing over weeks to months with elevated muscle enzymes, and the selective involvement pattern with shoulder girdle predominance fits this diagnosis 1, 3
Limb-Girdle Muscular Dystrophy (LGMD) can present in adult years with proximal weakness and elevated CK, but the rapidly progressive course over weeks to months is atypical for LGMD 1, 3

First-line investigations include CK and aldolase, myositis-specific autoantibodies panel, ESR, CRP, ANA, RF, and thyroid function and 25-OH vitamin D 1, 2, 3
Second-line investigations include EMG to confirm myopathic process, MRI of affected muscle groups, and muscle biopsy which is the gold standard for confirming inflammatory myopathy diagnosis and differentiating inflammatory from noninflammatory causes 1, 2, 3

Do not delay respiratory assessment - respiratory muscle involvement can rapidly progress to life-threatening failure in inflammatory myopathies 1, 2
Do not assume hereditary myopathy based on age alone - inflammatory myopathies commonly present in the third decade, and anti-HMGCR myopathy can mimic LGMD phenotype 3
Do not perform plasmapheresis immediately after IVIG as it will remove the immunoglobulin 2
Do not overlook cardiac involvement - obtain troponin and ECG as myocarditis can be life-threatening 2

If severe weakness (Grade 3-4), initiate methylprednisolone 1-2 mg/kg IV daily for severe inflammatory myositis while awaiting confirmatory testing, and consider plasmapheresis for acute or severe disease 2
If moderate weakness, hold statins immediately as they can contribute to myopathy, avoid medications that worsen neuromuscular weakness, and consider hospitalization for patients with severe weakness limiting mobility, respiratory involvement, or dysphagia 2