What is the best course of treatment for a 30-year-old female with recurring joint pain, iron deficiency anemia (IDA), and elevated platelets, with normal inflammatory markers and negative autoimmune screens?

Management of Recurrent Joint Pain with Iron Deficiency Anemia and Elevated Platelets

This patient requires comprehensive rheumatologic evaluation with additional autoimmune testing (RF, anti-CCP, HLA-B27) and iron replacement therapy, while recognizing that the elevated platelets are likely reactive to the iron deficiency and should normalize with treatment.

Diagnostic Approach to Joint Pain

Additional Rheumatologic Testing Required

• Complete RF (rheumatoid factor) and anti-CCP antibodies to evaluate for seronegative rheumatoid arthritis, as many patients with inflammatory arthritis can present with negative ANA but positive RF/anti-CCP 1
• HLA-B27 testing should be considered given the migratory pattern affecting multiple joints and the full-body episode, which could suggest reactive arthritis or spondyloarthropathy 1
• Inflammatory markers should be rechecked during an active episode, as CRP and ESR can be normal between flares in inflammatory arthritis 1

Physical Examination Priorities

• Examine all peripheral joints for synovitis (swelling, warmth, effusion) rather than just tenderness, as true inflammatory arthritis requires objective joint swelling 1
• Assess for enthesitis (inflammation at tendon/ligament insertions), particularly at the Achilles tendon and plantar fascia, which would support spondyloarthropathy 1
• Examine the spine and sacroiliac joints for range of motion limitations and tenderness 1

Imaging Considerations

• Plain radiographs of the hands should be obtained to evaluate for early erosive changes, as early recognition is critical to avoid irreversible joint damage 1
• Ultrasound or MRI of affected joints if there is persistent arthritis or clinical synovitis to differentiate inflammatory from non-inflammatory causes 1

Understanding the Elevated Platelets

Relationship to Iron Deficiency

• Thrombocytosis occurs in approximately 22% of patients with iron deficiency anemia and is a reactive phenomenon 2
• The elevated platelet count should normalize within 3 months of iron replacement therapy in most patients, with 72% showing decreased platelet counts after treatment 2
• This reactive thrombocytosis does not increase plasma viscosity or thrombotic risk in the same way as primary thrombocythemia 3

No Additional Workup Needed for Platelets

The elevated platelets are almost certainly reactive to the iron deficiency and do not require separate hematologic investigation at this time 2, 4. The mechanism involves downregulation of tubulin expression in platelets during iron deficiency 5.

Iron Deficiency Management

Treatment Protocol

• Initiate oral ferrous sulfate 200 mg twice daily as first-line therapy 1
• Continue iron supplementation for 3 months after correction of the anemia to replenish iron stores 1
• If oral iron is not tolerated, consider intravenous iron preparations (iron sucrose 200 mg over 10 minutes, or ferric carboxymaltose 1000 mg over 15 minutes) 1

Monitoring Strategy

• Check complete blood count at 2 weeks to confirm response (hemoglobin rise ≥10 g/L is highly suggestive of iron deficiency) 1
• Monitor blood counts at 3,6,12, and 24 months after normalization to detect recurrent iron deficiency 1
• Expect platelet count to decrease as iron stores are repleted 2

Investigation of Iron Deficiency Cause

• Bidirectional endoscopy (upper and lower GI) is warranted in a 30-year-old with iron deficiency anemia, even with normal inflammatory markers, to exclude occult GI blood loss, celiac disease, or inflammatory bowel disease 1, 6
• Celiac serology (tissue transglutaminase antibodies) should be checked, as celiac disease can cause both iron deficiency and inflammatory arthritis 1, 6
• Menstrual history should be thoroughly assessed, as heavy menstrual bleeding is a common cause of iron deficiency in premenopausal women 1

Treatment Approach for Joint Pain

Initial Symptomatic Management

• NSAIDs (ibuprofen or naproxen) at therapeutic doses for symptomatic relief during active episodes 1, 7
  • Important caveat: NSAIDs can cause GI bleeding and may worsen iron deficiency anemia 8, 9, 8
  • Use the lowest effective dose for the shortest duration 8, 9, 8
  • Consider gastroprotection with proton pump inhibitors if prolonged NSAID use is needed 8, 9

When to Escalate Treatment

• If symptoms persist beyond 4 weeks despite NSAIDs, initiate prednisone 10-20 mg daily 1
• If unable to taper corticosteroids below 10 mg daily after 6-8 weeks, consider disease-modifying antirheumatic drugs (DMARDs) such as hydroxychloroquine, methotrexate, or sulfasalazine 1

Rheumatology Referral Indications

• Refer to rheumatology if there is objective joint swelling (synovitis) on examination 1
• Refer if symptoms persist despite initial treatment or if additional autoimmune testing is positive 1
• Early referral is critical to prevent erosive joint damage in inflammatory arthritis 1

Common Pitfalls to Avoid

• Do not assume the joint pain is non-inflammatory based solely on normal CRP/ESR during an asymptomatic period—inflammatory markers can fluctuate 1
• Do not attribute all symptoms to iron deficiency—while fatigue may improve with iron replacement, true inflammatory arthritis requires specific treatment 1
• Do not overlook celiac disease, which can cause both iron deficiency and inflammatory arthritis, and would require a gluten-free diet rather than immunosuppression 1, 6
• Do not delay investigation of the iron deficiency cause—even in a young woman, GI pathology must be excluded 1