What are the cutaneous manifestations of iron deficiency anemia and how are they managed?

Cutaneous Manifestations of Iron Deficiency Anemia

Iron deficiency anemia presents with several characteristic skin, nail, and mucosal findings that can be identified on physical examination, including angular stomatitis, glossitis, koilonychia, blue sclerae, and pagophagia, though these specific manifestations occur in the minority of patients and physical examination is generally unremarkable in most cases. 1, 2

Specific Cutaneous and Mucosal Findings

Oral and Mucosal Changes

• Angular stomatitis (painful cracks or fissures at the corners of the mouth) is a classic manifestation of iron deficiency 1, 2
• Glossitis (inflamed, smooth, often painful tongue with loss of papillae) occurs as iron stores become depleted 1, 2
• These oral findings reflect impaired mucosal regeneration due to iron's essential role in cellular turnover 1

Nail Changes

• Koilonychia (spoon-shaped nails with central depression and raised edges) is a pathognomonic sign of chronic severe iron deficiency 1, 2
• Nail growth abnormalities and brittle nails can occur even before frank anemia develops 1
• These changes reflect structural and microchemical alterations in keratinocyte formation 3

Other Cutaneous Manifestations

• Blue sclerae (bluish discoloration of the whites of the eyes due to thinning of collagen) may be visible on examination 1, 2
• Skin defects and impaired wound healing can occur due to iron's role in collagen synthesis 1
• Generalized pallor of conjunctivae and mucous membranes is a late and insensitive finding 2
• Pruritus and chronically sustained inflammation have been associated with iron deficiency in some cases 3

Behavioral Manifestations Related to Iron Deficiency

• Pagophagia (compulsive ice craving and chewing) occurs in 40-50% of iron deficiency cases and often resolves rapidly with iron replacement 1, 2, 4
• Restless legs syndrome affects 32-40% of patients with iron deficiency 1, 2, 4
• Pica (craving for non-nutritive substances) may manifest beyond ice consumption 5

Clinical Context and Diagnostic Approach

When to Suspect Iron Deficiency

• These cutaneous findings should prompt investigation for iron deficiency, but their absence does not exclude the diagnosis 1
• Most patients with iron deficiency anemia have unremarkable physical examinations, making laboratory confirmation essential 1, 2
• Serum ferritin <30 ng/mL (in the absence of inflammation) or transferrin saturation <20% confirms iron deficiency 4

Hair Loss Considerations

• The relationship between iron deficiency and hair loss (including alopecia areata, androgenetic alopecia, and telogen effluvium) remains controversial with insufficient evidence for universal screening 6
• Some clinicians screen patients with hair loss for iron deficiency, though this practice is not evidence-based 6

Management of Cutaneous Manifestations

Iron Replacement Strategy

• Oral iron therapy (ferrous sulfate 325 mg daily or on alternate days) is first-line treatment for most patients and will resolve cutaneous manifestations as iron stores are repleted 4
• Symptoms like pagophagia often improve rapidly, even before hemoglobin normalizes 4
• Mucosal and nail changes typically resolve more slowly over months as tissues regenerate 1

When to Use Intravenous Iron

• Intravenous iron is indicated for patients with oral iron intolerance, malabsorption (celiac disease, post-bariatric surgery), chronic inflammatory conditions (IBD, CKD, heart failure), ongoing blood loss, or during second/third trimester pregnancy 4
• IV iron may lead to faster resolution of symptoms compared to oral therapy 1

Monitoring Response

• Hemoglobin should increase by approximately 1 g/dL every 2-3 weeks with adequate iron replacement 7
• Cutaneous manifestations should gradually improve as iron stores are repleted, with ferritin targets of 100 μg/L or higher in patients with inflammatory bowel disease 1
• Failure to respond warrants investigation for ongoing blood loss, malabsorption, or alternative diagnoses 6, 7

Critical Pitfalls to Avoid

• Do not assume cutaneous findings alone establish the diagnosis—laboratory confirmation with ferritin and/or transferrin saturation is mandatory 4
• Do not stop investigating after treating iron deficiency—the underlying cause (GI bleeding, celiac disease, menorrhagia) must be identified and addressed 1, 8
• Do not overlook celiac disease screening—it accounts for 3-5% of iron deficiency anemia cases and is easily missed 1, 8
• Do not accept minor dietary insufficiency as the sole explanation in men or postmenopausal women—bidirectional endoscopy is required to exclude GI malignancy 1, 8