In an 83-year-old man with one month of proximal muscle weakness, elevated C-reactive protein and erythrocyte sedimentation rate, normal creatine kinase, and low-titer positive antinuclear antibody, what is the most likely diagnosis?

Differential Diagnosis: Polymyalgia Rheumatica vs. Inflammatory Myositis

The most likely diagnosis is polymyalgia rheumatica (PMR), given the proximal muscle weakness (likely pain-limited rather than true weakness), markedly elevated inflammatory markers (CRP 73, ESR 74), normal CK, and age 83 years. 1, 2

Key Diagnostic Reasoning

Normal CK Rules Out True Myositis

• Normal creatine kinase is the critical distinguishing feature that excludes inflammatory myositis and points toward PMR. 1, 3, 2
• True myositis typically shows CK elevations with a median of approximately 2650 IU/L (range 335-20,270 IU/L), often >10 times the upper limit of normal in immune-mediated necrotizing myopathy. 4, 3
• PMR characteristically presents with severe myalgia and functional limitation that mimics weakness, but CK levels remain within normal limits because there is no actual muscle damage. 1, 2

Clinical Pattern Fits PMR

• The patient's age (83 years) falls within the typical PMR demographic, with average onset at 73 years. 5
• Proximal muscle involvement affecting shoulders and hips is the hallmark of PMR, though what appears as "weakness" is actually pain-limited movement rather than true motor weakness. 2, 5, 6
• Markedly elevated inflammatory markers (ESR 74, CRP 73) are present in over 90% of PMR cases and support the diagnosis. 5, 7

Low-Titer ANA (1:160) is Non-Specific

• The ANA titer of 1:160 is low and non-specific in an elderly patient, and does not suggest a primary autoimmune connective tissue disease. 2
• This level of ANA positivity can occur in normal elderly individuals and does not alter the PMR diagnosis. 2

Critical Next Steps

Confirm True Weakness vs. Pain-Limited Movement

• Perform a careful physical examination to distinguish true motor weakness from pain-limited movement. 1, 2
• In PMR, patients have full strength when pain is controlled, whereas true myositis shows objective motor weakness on manual muscle testing. 4, 1
• Ask specifically about bilateral shoulder and hip girdle pain with severe morning stiffness (>45 minutes), which is pathognomonic for PMR. 2, 5, 6

Screen for Giant Cell Arteritis (GCA)

• Immediately assess for GCA symptoms, as 20% of PMR patients have concurrent GCA, which requires higher-dose glucocorticoids to prevent blindness. 4, 2, 5
• Ask about new headache, jaw claudication, visual changes (diplopia, amaurosis fugax), scalp tenderness, and temporal artery tenderness. 4, 6
• If any GCA features are present, start prednisone 40-60 mg daily immediately and arrange urgent temporal artery ultrasound or biopsy. 4, 6

Exclude PMR Mimics

• Complete the baseline laboratory workup to exclude conditions that mimic PMR: 2
  • Rheumatoid factor and anti-CCP antibodies to exclude elderly-onset rheumatoid arthritis (most common PMR mimic). 2, 8
  • Complete blood count to assess for anemia, thrombocytosis, or hematologic malignancy. 2, 8
  • Comprehensive metabolic panel (glucose, creatinine, liver enzymes) for baseline before glucocorticoid therapy. 2
  • Thyroid-stimulating hormone (TSH) to exclude thyroid disorders. 2
  • Protein electrophoresis to exclude paraproteinemia/multiple myeloma. 2, 8
  • Consider chest X-ray to exclude malignancy, as solid tumors can present with polymyalgia symptoms. 2, 8

Additional Muscle Enzyme Testing if Uncertainty Remains

• If clinical suspicion for myositis persists despite normal CK, measure aldolase, AST, ALT, and LDH, as one may be elevated when CK is normal. 1, 3
• Consider muscle MRI or biopsy only if additional muscle enzymes are elevated or true weakness is confirmed on examination. 1, 3

Therapeutic Trial as Diagnostic Confirmation

• Initiate prednisone 15-20 mg daily (within the recommended 12.5-25 mg range for this elderly patient). 2
• PMR responds dramatically within 48-72 hours, with near-complete resolution of symptoms within 1-2 weeks. 2, 5, 6
• Lack of rapid, dramatic improvement should prompt immediate reassessment of the diagnosis and consideration of alternative conditions. 2, 8

Common Pitfalls to Avoid

• Do not confuse pain-limited movement with true motor weakness—this is the most common diagnostic error leading to misdiagnosis of myositis. 1, 2
• Do not miss concurrent GCA—always screen for cranial symptoms, as 20% of PMR patients have GCA requiring higher glucocorticoid doses. 4, 5, 6
• Do not start prednisone <12.5 mg daily—subtherapeutic dosing leads to persistent symptoms and diagnostic uncertainty. 2
• Do not overlook malignancy—solid tumors and hematologic malignancies can present with polymyalgia symptoms, especially if response to glucocorticoids is poor or atypical features are present. 2, 8
• Do not forget osteoporosis prophylaxis—start calcium 1200-1500 mg and vitamin D 800-1000 IU daily immediately, with bisphosphonate therapy for this elderly patient. 2

Alternative Diagnoses to Consider if PMR is Excluded

• Elderly-onset rheumatoid arthritis if RF/anti-CCP positive or peripheral joint synovitis develops. 2, 8
• Seronegative symmetrical polyarthritis (SSP) if hand arthritis develops during follow-up (can occur in 5% of cases initially presenting as PMR). 8
• Malignancy (solid tumor or hematologic) if poor response to appropriate-dose glucocorticoids or constitutional symptoms predominate. 2, 8
• Hypothyroidism if TSH is elevated. 2
• Statin-induced myopathy if patient is on statins, though CK would typically be elevated. 4