What are the symptoms and treatment options for iron deficiency, particularly in women of childbearing age with heavy menstrual bleeding or those with a history of gastrointestinal disorders like celiac disease or Crohn's disease?

Iron Deficiency: Symptoms and Clinical Manifestations

Iron deficiency presents with a spectrum of symptoms ranging from subtle fatigue and cognitive impairment to severe anemia with cardiopulmonary compromise, and the clinical presentation varies dramatically based on the rate of development and severity of deficiency. 1

Symptom Categories by Severity

Non-Anemic Iron Deficiency (Early Stage)

• Fatigue and decreased exercise tolerance are often the earliest and most common symptoms, occurring even before anemia develops 1, 2
• Cognitive symptoms including difficulty concentrating, irritability, and depression affect many patients with iron depletion alone 1, 3
• Restless legs syndrome occurs in 32-40% of iron-deficient patients and may be the presenting complaint 1
• Hair loss is a frequently overlooked manifestation of iron deficiency 2

Iron Deficiency Anemia (Advanced Stage)

• Cardiopulmonary symptoms including dyspnea, palpitations, tachycardia, and lightheadedness develop as hemoglobin falls 1, 3
• Angina and worsening heart failure can occur in patients with pre-existing cardiac disease, even with moderate anemia 1, 3
• Pica (craving for non-food substances like ice, dirt, or starch) affects 40-50% of patients with established iron deficiency anemia 1
• Orthopnea and edema may develop in severe cases with cardiac decompensation 3

Pediatric-Specific Manifestations

• Skin or conjunctival pallor is the most visible sign in children 3
• Learning disabilities, diminished attention span, and inappropriate behavior reflect the impact on neurodevelopment 3
• Excessive sleepiness and tiredness interfere with normal childhood activities 3

Physical Examination Findings

Laboratory Manifestations

• Microcytosis (MCV below normal range) is characteristic but may be absent with concurrent folate deficiency 4
• Serum ferritin <12 μg/dL is diagnostic of iron deficiency, though ferritin 12-100 μg/dL can still indicate deficiency in the presence of inflammation, malignancy, or hepatic disease 4
• Transferrin saturation <20-30% supports the diagnosis when ferritin is equivocal 4, 1
• Hemoglobin <13 g/dL in men and <12 g/dL in women defines anemia, though symptoms can occur at higher levels 5, 1

Population-Specific Considerations

Women of Childbearing Age with Heavy Menstrual Bleeding

• Menstrual blood loss causes an average additional 0.3-0.5 mg daily iron loss during reproductive years 4
• 38% of nonpregnant reproductive-age women have iron deficiency without anemia, and 13% have iron deficiency anemia in high-income countries 1
• During third trimester pregnancy, up to 84% develop iron deficiency due to increased demands 1
• Menorrhagia is the most common cause in premenopausal women, though gastrointestinal pathology must still be excluded, particularly in those over 40-45 years 4, 6

Patients with Gastrointestinal Disorders

Celiac Disease

• Celiac disease accounts for 3-5% of all iron deficiency anemia cases and must be screened in every patient with unexplained anemia 6, 7, 5
• Malabsorption occurs even without classic gastrointestinal symptoms, making serological screening with tissue transglutaminase antibody (IgA type) plus total IgA level mandatory 7, 5, 8
• Upper endoscopy with duodenal biopsies is required if serology is positive or clinical suspicion remains high 6, 5

Crohn's Disease and Inflammatory Bowel Disease

• 13-90% of IBD patients develop iron deficiency due to chronic inflammation, malabsorption, and occult bleeding 1
• Recurrent iron deficiency may indicate ongoing inflammatory activity even with clinical remission and normal biomarkers 6
• Crohn's disease is a common cause of iron deficiency in young adults and should be investigated with bidirectional endoscopy 4

Critical Diagnostic Pitfalls

Common Missed Diagnoses

• NSAID use (including over-the-counter ibuprofen, naproxen, aspirin) causes occult gastrointestinal blood loss even without overt bleeding symptoms, and patients frequently fail to report these medications 6, 7, 5
• Anticoagulants and antiplatelet agents can unmask underlying vascular lesions like angiodysplasia 6
• Dietary history alone should never be accepted as the sole cause—full gastrointestinal investigation is still required even with documented poor intake 4
• Failing to screen for celiac disease results in missed diagnoses in 3-5% of cases 6, 7

Investigation Requirements

• In men and postmenopausal women, gastrointestinal blood loss is the predominant mechanism requiring urgent bidirectional endoscopy to exclude malignancy 6, 9
• Upper GI endoscopy reveals a cause in 30-50% of patients, and colonoscopy must also be performed as dual pathology exists in 10-15% 6, 7
• Do not stop investigating after finding one cause—multiple etiologies coexist frequently 6, 7

Treatment Approach

Oral Iron Therapy

• Ferrous sulfate 200-325 mg (containing 65 mg elemental iron) three times daily is first-line treatment 4, 10, 1
• Adding vitamin C 500 mg with each iron dose enhances absorption 4, 7
• Continue iron for 3 months after hemoglobin normalizes to replenish body stores, targeting ferritin >50 ng/mL 4, 7
• Hemoglobin should rise by 2 g/dL after 3-4 weeks—failure indicates poor compliance, continued blood loss, malabsorption, or misdiagnosis 4
• Every-other-day dosing improves absorption and reduces side effects in patients with gastrointestinal intolerance 9

Intravenous Iron Indications

• Intolerance to at least two oral preparations or documented non-compliance 4
• Malabsorption conditions including celiac disease, post-bariatric surgery, atrophic gastritis, or inflammatory bowel disease 1, 8, 9
• Ongoing blood loss that cannot be controlled 1
• Chronic inflammatory conditions including chronic kidney disease, heart failure, or cancer 1, 9
• Second and third trimesters of pregnancy 1, 9
• Heart failure patients to increase exercise capacity 9

Monitoring Strategy

• Evaluate response to oral iron in 2-4 weeks with repeat hemoglobin and ferritin 9
• Monitor hemoglobin and MCV every 3 months for one year, then annually after correction 4
• Additional oral iron is indicated if hemoglobin or MCV falls below normal during follow-up 4
• Further investigation is only necessary if hemoglobin and MCV cannot be maintained with supplementation 4