What is the next step in managing a 48-year-old female with proximal muscle weakness, headaches, scalp tenderness, shoulder stiffness and pain, and nonspecific lower abdominal pain, with normal Complete Blood Count (CBC), Erythrocyte Sedimentation Rate (ESR), and C-Reactive Protein (CRP) levels?

Management of Suspected Polymyalgia Rheumatica with Normal Inflammatory Markers

Despite normal ESR and CRP, this patient's clinical presentation—proximal muscle weakness, shoulder stiffness and pain, and scalp tenderness—strongly suggests polymyalgia rheumatica (PMR) with possible giant cell arteritis (GCA), and you should proceed with temporal artery imaging or biopsy while simultaneously initiating glucocorticoid therapy if GCA features are present.

Immediate Diagnostic Priorities

Rule Out Giant Cell Arteritis First

The combination of headaches and scalp tenderness in this patient raises critical concern for GCA, which can cause irreversible blindness if untreated. 1

Key clinical features demanding urgent GCA evaluation:

• New-onset headaches with scalp tenderness are cranial arteritis symptoms 1
• Visual symptoms must be specifically queried (any vision changes, jaw claudication, tongue pain) 1
• Treatment should not be delayed for diagnostic procedures if GCA is suspected 1

Immediate actions for GCA concern:

• Obtain temporal artery ultrasound (color duplex) or arrange temporal artery biopsy 2
• If any visual symptoms or high clinical suspicion exists, start prednisone 40-60 mg/day immediately before biopsy 2, 3
• Refer urgently to ophthalmology if any visual disturbances present 1

Understanding Normal Inflammatory Markers in PMR/GCA

Normal ESR and CRP do not exclude PMR or GCA. 1

The 2024 EULAR/ACR guidelines explicitly state that relapses may occur despite normal inflammatory markers, and the 2015 EULAR/ACR recommendations recognize PMR with normal ESR as an atypical presentation warranting specialist referral. 1, 4

• A documented case series confirms GCA can present with completely normal inflammatory markers yet show positive temporal artery biopsy 5
• Clinical presentation takes precedence over laboratory values in diagnosis 5, 6
• Normal inflammatory markers increase diagnostic complexity but should not prevent appropriate treatment 4

Diagnostic Workup for PMR

Complete the following laboratory panel immediately: 1

• Repeat ESR and CRP (may become elevated during follow-up even if initially normal) 4
• Rheumatoid factor (RF) and anti-CCP antibodies (to exclude rheumatoid arthritis) 1
• Creatine kinase (CK) (must be normal to differentiate from myositis) 1
• Complete blood count, glucose, creatinine, liver function tests 1
• Calcium, alkaline phosphatase, vitamin D (baseline for glucocorticoid monitoring) 1
• Thyroid stimulating hormone (TSH) (exclude thyroid disease mimicking PMR) 1
• Urinalysis 1

Additional testing to consider based on clinical context: 1

• Protein electrophoresis (exclude myeloma in elderly)
• ANA, ANCA (if features suggest vasculitis or connective tissue disease)
• Chest radiograph (exclude malignancy, infection)

Critical Differential Diagnoses to Exclude

The nonspecific lower abdominal pain adds complexity and requires consideration of:

Musculoskeletal mimics: 1, 6

• Rotator cuff disease, adhesive capsulitis (can coexist with PMR)
• Osteoarthritis of shoulders/hips
• Cervical or lumbar radiculopathy

Systemic conditions requiring exclusion: 1, 3

• Seronegative rheumatoid arthritis (check RF, anti-CCP, look for peripheral synovitis)
• Inflammatory myositis (CK must be normal in PMR)
• Malignancy (paraneoplastic syndrome)
• Endocrine disorders (hypothyroidism, hyperparathyroidism)
• Infection (endocarditis, chronic infections)

The abdominal pain specifically requires:

• Evaluation for intra-abdominal malignancy
• Assessment for large vessel vasculitis involving abdominal aorta (if GCA confirmed)
• Consideration of unrelated gynecologic pathology

Treatment Approach

If GCA Features Present (Headaches + Scalp Tenderness)

Start high-dose glucocorticoids immediately: 2, 3

• Prednisone 40-60 mg/day orally
• Do not delay for biopsy results (biopsy remains positive for weeks after starting treatment) 1
• Consider tocilizumab addition per FDA approval for GCA 2

If Pure PMR Without GCA Features

Initiate moderate-dose glucocorticoids: 1, 2

• Prednisone 10-20 mg/day
• Expect dramatic improvement within 1-3 days (lack of response questions diagnosis) 1, 6
• If no improvement after 1 week, reconsider diagnosis 6

Glucocorticoid management principles: 1

• Taper slowly over 4-6 weeks once symptoms controlled
• Monitor for relapse (occurs in up to 60% of patients) 1
• Consider methotrexate as steroid-sparing agent if prolonged therapy needed or high relapse risk 2

Specialist Referral Indications

Refer to rheumatology for: 1, 4

• Atypical presentation (normal inflammatory markers qualifies) 1, 4
• Age <60 years 1
• Peripheral inflammatory arthritis 1
• Inability to taper prednisone below 10 mg/day after 3 months 1
• Relapses or refractory disease 1

Monitoring Strategy

Clinical and laboratory monitoring required: 1

• ESR and CRP should be monitored during follow-up even if initially normal 4
• Assess for glucocorticoid-related adverse effects (osteoporosis, diabetes, hypertension, cataracts) 1
• Monitor for disease relapse symptoms 1
• Document comorbidities and initiate bone protection (calcium, vitamin D, bisphosphonates if indicated) 1

Common Pitfalls to Avoid

• Never dismiss GCA/PMR diagnosis based solely on normal inflammatory markers 1, 5
• Do not delay glucocorticoid therapy in suspected GCA awaiting biopsy 1
• Do not assume shoulder pain is purely PMR without excluding rotator cuff disease 1
• Do not use NSAIDs alone as therapeutic trial—they are insufficient for PMR 1, 6
• Do not forget that fatigue can be disease-related, treatment-related, or from other conditions 1