What is the best course of treatment for a 30-year-old female patient with progressively worsening headaches over 7 months, subsequent joint pain, iron deficiency anemia, and improvement with prednisone, despite normal inflammatory markers, negative autoimmune workup, and negative tick panel?

Diagnostic Evaluation for Giant Cell Arteritis (Temporal Arteritis)

This patient requires urgent evaluation for giant cell arteritis (GCA), given the combination of progressively worsening headaches over 7 months, joint pain (polymyalgia rheumatica pattern), dramatic response to prednisone, and iron deficiency anemia—all classic features of this vasculitis that can cause permanent vision loss within days if untreated.

Critical Diagnostic Steps

Immediate Clinical Assessment

• Check specifically for temporal arteritis symptoms: headache (especially new-onset or changed pattern), visual disturbances, jaw claudication (pain with chewing), scalp tenderness, and temporal artery abnormalities on palpation 1
• Urgent ophthalmologic evaluation is mandatory if any visual symptoms are present, as permanent visual loss can occur within days of symptom onset 1
• Examine temporal arteries bilaterally for tenderness, nodularity, or decreased pulsation 1

Laboratory Workup

• Inflammatory markers (ESR and CRP) are essential, though normal values do not exclude GCA—approximately 10-20% of biopsy-proven cases have normal inflammatory markers 1
• Complete blood count to characterize the iron deficiency anemia, which is common in GCA due to chronic inflammation 2, 3
• Serum ferritin, iron studies, and transferrin saturation to distinguish iron deficiency from anemia of chronic disease, noting that ferritin thresholds may need to be higher in inflammatory conditions 2, 3
• Autoimmune panel including ANA, RF, anti-CCP to exclude other rheumatologic conditions, though these are typically negative in GCA 1

Temporal Artery Biopsy

• Proceed with temporal artery biopsy as the gold standard for diagnosis, ideally within 1-2 weeks of starting corticosteroids (though treatment should never be delayed for biopsy) 1
• Biopsy remains positive for several weeks after corticosteroid initiation 1

Treatment Algorithm

Immediate Management (Before Biopsy Results)

Initiate prednisone 40-60 mg daily immediately if clinical suspicion for GCA is high, particularly with any visual symptoms or jaw claudication 1

• Do not delay treatment while awaiting biopsy or test results—permanent vision loss is preventable with prompt corticosteroid therapy 1
• If visual symptoms are present, consider starting with IV methylprednisolone 1 gram daily for 3 days before transitioning to oral prednisone 1

Corticosteroid Tapering Strategy

• Continue initial dose for 2-4 weeks until symptoms resolve and inflammatory markers normalize 1
• Taper slowly over 4-6 weeks to prednisone 20 mg daily, then reduce by 2.5 mg every 2-4 weeks 1
• Monitor ESR and CRP every 4-6 weeks during taper to detect disease flare 1
• Total treatment duration typically 12-24 months 1

Corticosteroid-Sparing Agents

• Consider methotrexate or tocilizumab (IL-6 inhibitor) if unable to taper prednisone below 10 mg daily after 3 months, or if significant corticosteroid-related side effects develop 1
• Tocilizumab is particularly effective for GCA but requires caution regarding intestinal perforation risk 1
• Screen for hepatitis B, C, and latent tuberculosis before initiating any immunosuppressive therapy 1

Management of Iron Deficiency Anemia

Diagnostic Approach

• Distinguish between true iron deficiency and anemia of chronic disease using ferritin and transferrin saturation 2, 3
• In inflammatory conditions like GCA, ferritin <100 ng/mL with transferrin saturation <20% suggests true iron deficiency 3
• Investigate sources of blood loss (gastrointestinal, menstrual) even in the setting of chronic inflammation 2

Iron Supplementation

• Oral iron supplementation (ferrous sulfate 325 mg daily) is first-line for mild anemia without active inflammation 2
• Intravenous iron (ferric carboxymaltose) is preferred if:
  • Oral iron is not tolerated or ineffective after 4-6 weeks 2
  • Hemoglobin <10 g/dL 2
  • Active inflammation is present, as oral iron absorption is impaired 4, 3
• IV iron does not worsen inflammatory markers in chronic inflammatory conditions 4

Monitoring and Follow-Up

• Serial rheumatologic examinations every 4-6 weeks including inflammatory markers (ESR, CRP) after treatment initiation 1
• Repeat hemoglobin and iron studies at 4-6 weeks to assess response to iron supplementation 2
• Monitor for corticosteroid complications: bone density screening, glucose monitoring, PCP prophylaxis if prednisone >20 mg for >12 weeks 1
• Ophthalmologic follow-up if any visual symptoms were present 1

Critical Pitfalls to Avoid

• Never delay corticosteroid therapy while awaiting temporal artery biopsy—permanent blindness can occur within days 1
• Do not rely solely on normal inflammatory markers to exclude GCA—10-20% of cases have normal ESR/CRP 1
• Do not taper corticosteroids too rapidly—disease flares are common with premature tapering 1
• Do not overlook the joint pain as separate from GCA—polymyalgia rheumatica occurs in 40-60% of GCA patients and responds to the same corticosteroid regimen 1
• Do not attribute all anemia to chronic disease—investigate and treat concurrent iron deficiency, which worsens quality of life and may impair response to GCA treatment 5, 6