What is the differential diagnosis and management for iron deficiency anemia (IDA) with itching?

Iron Deficiency Anemia with Itching: Differential Diagnosis and Management

When a patient presents with iron deficiency anemia and itching, the itching is unlikely to be directly caused by the anemia itself—instead, focus your differential diagnosis on underlying conditions that can cause both symptoms, particularly gastrointestinal pathologies, celiac disease, and inflammatory bowel disease. 1

Key Differential Diagnoses to Consider

Gastrointestinal Pathologies

• Colorectal or gastric malignancy can present with iron deficiency anemia and may cause pruritus through paraneoplastic mechanisms or cholestasis from liver involvement 1, 2
• Celiac disease is found in 2-5% of iron deficiency anemia cases and commonly presents with dermatitis herpetiformis (intensely pruritic vesicular rash) as an extraintestinal manifestation 1, 2
• Inflammatory bowel disease (particularly ulcerative colitis) causes anemia in 40-66% of patients and can present with pruritic skin manifestations 1

Other Causes Linking Both Symptoms

• Chronic kidney disease can cause both anemia and uremic pruritus 3
• Cholestatic liver disease may present with pruritus and anemia from chronic gastrointestinal blood loss or malabsorption 1
• Polycythemia vera (paradoxically can have iron deficiency from chronic phlebotomy/bleeding) classically presents with aquagenic pruritus, though this is less common 3

Diagnostic Approach

Initial Laboratory Evaluation

• Confirm iron deficiency with serum ferritin <30 mcg/L (or <100 mcg/L if inflammation present) and transferrin saturation <16% 1
• Screen for celiac disease with tissue transglutaminase antibody (IgA) and total IgA levels—this is mandatory given the pruritic presentation 1, 4
• Check inflammatory markers (CRP, ESR) to distinguish absolute iron deficiency from anemia of chronic disease 1
• Assess renal function and liver function tests to evaluate for systemic causes 4

Endoscopic Investigation

• Bidirectional endoscopy (gastroscopy and colonoscopy) is strongly recommended for all men and postmenopausal women with unexplained iron deficiency anemia, as approximately one-third have underlying GI pathology 1, 2
• Obtain small bowel biopsies during upper endoscopy even if mucosa appears normal, as celiac disease is present in 2-3% of cases and can explain both anemia and pruritus (dermatitis herpetiformis) 1, 5
• For premenopausal women, the American Gastroenterological Association suggests (conditional recommendation) bidirectional endoscopy over iron replacement alone, particularly when symptoms like pruritus suggest underlying pathology 1

Additional Testing Based on Initial Results

• If bidirectional endoscopy is negative and the patient has severe or transfusion-dependent anemia with persistent pruritus, consider capsule endoscopy to evaluate the small bowel for occult bleeding sources or inflammatory conditions 1, 2
• Test for Helicobacter pylori non-invasively if suspected, as it can cause iron malabsorption and gastric pathology 1, 6
• Urinalysis to exclude urinary tract bleeding as a source 5, 4

Management Strategy

Iron Replacement

• Initiate oral ferrous sulfate 200 mg three times daily (65 mg elemental iron per dose) regardless of the investigation results, as treatment should not be delayed 5
• Expect hemoglobin to rise ≥10 g/L within 2 weeks; if this does not occur, consider malabsorption, ongoing blood loss, or misdiagnosis 1, 5
• Continue iron supplementation for 3 months after hemoglobin normalizes to replenish body stores 1, 5

Treat Underlying Cause

• If celiac disease is confirmed (positive serology and small bowel biopsy), initiate strict gluten-free diet—this will address both the anemia and pruritus (dermatitis herpetiformis) 1, 4
• If inflammatory bowel disease is diagnosed, manage according to disease severity with appropriate anti-inflammatory therapy 1
• If malignancy is found, urgent referral for oncologic management is required 1

Follow-Up Monitoring

• Monitor hemoglobin and MCV every 3 months for 1 year, then recheck after an additional year 1, 5
• If anemia recurs or pruritus persists despite treatment, further investigation is warranted—do not accept initial negative findings as definitive 1, 2

Critical Clinical Pitfalls

• Do not attribute pruritus to iron deficiency anemia itself—itching is not a typical symptom of uncomplicated iron deficiency and should prompt investigation for alternative or coexisting diagnoses 3
• Multiple causes frequently coexist (e.g., celiac disease with concurrent GI malignancy occurs in 10-15% of cases), so finding one explanation should not stop further investigation if symptoms persist 1, 2
• Serum ferritin can be falsely normal in inflammatory conditions (acts as acute phase reactant); use a threshold of 100 mcg/L in the presence of inflammation 1
• Do not rely on fecal occult blood testing—it is insensitive and non-specific for diagnosing the cause of iron deficiency anemia 1