What are the cutaneous manifestations of severe anemia in patients, particularly the elderly or those with underlying chronic diseases?

Cutaneous Manifestations of Severe Anemia

The most clinically significant cutaneous manifestation of severe anemia is pallor of the conjunctiva, palms, and nail beds, which can reliably detect severe anemia (hemoglobin <70 g/L) with >84% specificity when assessed at multiple anatomical sites. 1

Primary Cutaneous Findings in Severe Anemia

Pallor (Most Common and Diagnostically Useful)

• Pallor of the conjunctiva, palms, and nail beds is the hallmark cutaneous sign of severe anemia, with individuals showing significantly lower hemoglobin concentrations when pallor is present at any of these sites 1
• The sensitivity of pallor for detecting severe anemia varies by population (29-81%), but specificity consistently exceeds 84%, making it a useful screening tool where severe anemia is prevalent 1
• Multiple anatomical sites should be assessed simultaneously (conjunctiva, palms, and nail beds) rather than relying on a single site, as the relative performance of different sites varies among populations 1
• Pallor assessment by non-physician health workers is feasible and worthwhile in primary care settings where severe anemia is common 1

Disease-Specific Cutaneous Manifestations

When severe anemia is accompanied by specific cutaneous findings, consider rare genetic disorders:

Cutaneous Photosensitivity with Anemia

• Painful cutaneous photosensitivity (erythema, stinging, burning of sun-exposed skin) beginning in childhood with mild microcytic anemia suggests erythropoietic protoporphyria (EPP) 2

• EPP presents with 20-60% of patients showing microcytic anemia with mean hemoglobin decrease of 1.2 g/dL and reduced iron stores 2

• Fluorescent erythrocytes can be visualized in fresh, unstained blood smears 2

• Bullous cutaneous photosensitivity starting in early infancy with severe microcytic hypochromic hemolytic anemia indicates congenital erythropoietic porphyria (CEP) 2

• CEP presents with lifelong photosensitivity leading to scarring with photomutilation, hypertrichosis, erythrodontia (red teeth), and passage of red urine 2

• Approximately 66% of CEP patients suffer from chronic hemolytic anemia with variable severity 2

Necrotizing Panniculitis

• Necrotizing panniculitis (painful subcutaneous nodules with ulceration and drainage of clear, yellow, oily fluid) in the context of severe anemia should prompt evaluation for alpha-1 antitrypsin deficiency 2
• This occurs in approximately 1 per 1,000 cases of alpha-1 antitrypsin deficiency and can be lethal 2
• Trauma may precipitate the disease in approximately one-third of patients 2

Systemic Vasculitis

• Cutaneous vasculitis (erythematous or necrotizing papules, vesicles, palpable purpura, subcutaneous nodules, erythematous plaques, or ulcerative panniculitis) with severe anemia suggests systemic necrotizing vasculitis in alpha-1 antitrypsin deficiency 2
• These patients typically have multiple organ involvement (median of 8 organs affected) with fatal outcomes 2
• Necrotizing and leukocytoclastic vasculitis are the most frequent histopathological findings 2

Clinical Approach to Cutaneous Findings in Severe Anemia

Initial Assessment

• Examine conjunctiva, palms, and nail beds systematically for pallor in all patients with suspected severe anemia 1
• Document the presence or absence of photosensitivity, skin lesions, or subcutaneous nodules 2
• Assess for signs of chronic hemolysis (jaundice, splenomegaly) if cutaneous photosensitivity is present 2

When to Suspect Genetic Disorders

• Consider EPP when unexplained mild normocytic to microcytic anemia is accompanied by painful photosensitivity in childhood with low to normal serum ferritin 2
• Consider CEP when unexplained hemolytic anemia is combined with painful cutaneous photosensitivity, particularly if severe microcytic hypochromic anemia is present 2
• Confirm EPP diagnosis with fluorescent erythrocytes and/or enhanced protoporphyrin in plasma/erythrocytes 2
• Confirm CEP diagnosis with increased urinary uroporphyrin I and coproporphyrin I levels 2

Important Caveats

• The prevalence of pallor does not directly correspond to the prevalence of anemia or severe anemia in different populations, so clinical context matters 1
• Pallor is more sensitive in postpartum women (81%) compared to preschool children (29%), requiring lower threshold for laboratory confirmation in pediatric populations 1
• Many individuals without severe anemia will also demonstrate pallor, but the low cost of treating false positives is justified by the benefits of detecting true cases where severe anemia is common 1
• In elderly patients with anemia and underlying chronic diseases, cutaneous manifestations may be subtle due to gradual onset allowing physiologic compensation 2, 3