What is the diagnosis and treatment for a patient with anemia, pruritus (itching) on palms, and fatigue?

Diagnosis and Management of Anemia with Palmar Pruritus and Fatigue

The most critical step is to immediately evaluate for iron deficiency anemia (IDA) with bidirectional endoscopy to exclude gastrointestinal malignancy, while simultaneously screening for celiac disease, as these represent life-threatening causes that require urgent intervention. 1

Initial Diagnostic Workup

Laboratory Assessment

• Complete blood count (CBC) with mean corpuscular volume (MCV) to classify the anemia as microcytic, normocytic, or macrocytic 2, 3
• Iron panel including ferritin, serum iron, total iron-binding capacity, and transferrin saturation 1, 2
• Inflammatory markers (CRP and ESR) to distinguish pure IDA from anemia of chronic disease 1
• Celiac disease screening with tissue transglutaminase antibody (IgA) and total IgA level before endoscopy 1
• Vitamin B12 and folate levels to exclude megaloblastic anemia 4, 2
• Reticulocyte count to assess bone marrow response 4, 2

Critical Physical Examination Findings

• Assess pallor of palms, conjunctivae, and nailbeds - palm pallor has 95% sensitivity for moderate anemia (hemoglobin <8 g/dL) but only 64-68% specificity 5
• Conjunctival pallor is more specific (81%) and should be prioritized over palm assessment 5
• Evaluate for systolic ejection murmur, altered sensorium, or splenomegaly - these findings independently predict severe anemia and warrant urgent referral 5

Palmar Pruritus Considerations

The combination of anemia and palmar itching raises concern for several specific diagnoses:

• Polycythemia vera (though this causes elevated hemoglobin, not anemia, making it less likely here)
• Cholestatic liver disease with secondary anemia - check liver function tests and bile acids 6
• Uremic pruritus from chronic kidney disease - check urea, creatinine, and electrolytes 6
• Iron deficiency itself can cause pruritus independent of anemia severity 6

Immediate Management Based on Severity

Severe Anemia (Hemoglobin <8 g/dL or symptomatic)

• Intravenous iron is first-line treatment for severe IDA 1
• Target hemoglobin normalization and ferritin >100 μg/L 1, 6
• Consider blood transfusion if hemoglobin <7 g/dL or patient is hemodynamically unstable 7
• Avoid oral iron initially in severe cases due to poor absorption and slower response 1

Moderate Anemia (Hemoglobin 8-10 g/dL)

• Oral or IV iron replacement depending on tolerability and urgency 1
• Monitor hemoglobin and reticulocyte count at 5-7 days, then frequently until normalized 4
• If reticulocytes fail to increase appropriately, reevaluate diagnosis and consider complicating factors like folate deficiency or chronic disease 4

Mandatory Gastrointestinal Evaluation

Bidirectional endoscopy (upper endoscopy and colonoscopy) is mandatory for all adults with IDA to exclude malignancy, particularly in patients with family history of GI cancer 1. This is non-negotiable even if other causes seem apparent.

Additional GI Considerations

• Celiac disease is found in 3-5% of IDA cases and must be screened before endoscopy 1
• Angiodysplasia is common in elderly patients as a source of occult bleeding 1
• If malignancy is identified, immediate surgical or oncological referral is required 1

Management of Persistent Symptoms

If Bicytopenia Develops or Persists

• Bone marrow biopsy is indicated after iron repletion to exclude myelodysplastic syndrome or marrow infiltration 1
• Erythropoiesis-stimulating agents (ESAs) may be considered only if anemia of chronic disease is confirmed with inadequate response to IV iron, targeting hemoglobin ≤12 g/dL 1

Vitamin B12 Deficiency Management (if identified)

• Intramuscular vitamin B12 100 mcg daily for 6-7 days, then alternate days for 7 doses, then every 3-4 days for 2-3 weeks 4
• Maintenance: 100 mcg monthly for life 4
• Critical warning: Folic acid >0.1 mg daily can mask B12 deficiency hematologically while allowing irreversible neurologic damage to progress 4

Pruritus-Specific Treatment

• Optimize dialysis adequacy if uremic (target Kt/V ~1.6) 6
• Emollients are essential for xerosis-associated pruritus 6
• Topical capsaicin 0.025% four times daily for 4 weeks showed marked relief in 82% of patients with uremic pruritus 6
• Correct anemia with erythropoietin if uremic, as this may improve pruritus 6

Monitoring and Prevention

Follow-up Schedule

• Monitor for recurrent iron deficiency every 3 months for at least one year after correction, then every 6-12 months 6
• Reinitiate IV iron when ferritin drops below 100 μg/L or hemoglobin falls below 12-13 g/dL (gender-dependent) 6
• Rapid recurrence suggests subclinical inflammatory activity even with normal CRP 6

Fatigue Management

Fatigue is the cardinal symptom of anemia and directly correlates with hemoglobin levels 8. However, fatigue may persist even after hemoglobin normalization if:

• Iron stores remain depleted (ferritin <100 μg/L) 6
• Vitamin D, IGF-1, or magnesium deficiency coexists 6
• Underlying inflammatory disease remains active 6

Common Pitfalls to Avoid

• Never give folic acid without checking B12 first - this can precipitate irreversible spinal cord degeneration in B12 deficiency 4
• Do not skip endoscopy even if iron deficiency seems explained by menstruation or diet 1
• Avoid IV administration of vitamin B12 - almost all will be lost in urine; use IM route 4
• Do not rely solely on palm pallor for severity assessment - use conjunctival examination for better specificity 5
• Recognize that pruritus may be the only sign of disease activity in inflammatory conditions like IBD 6