What causes blue and grey skin discoloration?

Causes of Blue and Grey Skin Discoloration

Blue and grey skin discoloration is primarily caused by methemoglobinemia, cyanosis due to poor tissue oxygenation, vascular disorders, drug reactions, and metal deposition in the skin. 1, 2, 3, 4

Methemoglobinemia

Methemoglobinemia is a major cause of blue-grey skin discoloration, characterized by elevated levels of methemoglobin (MetHb) in the blood:

Congenital Causes

• Type I (NADH-cytochrome b5 reductase deficiency):

  • Presents with blue discoloration from birth
  • MetHb levels typically 20-30%
  • Lavender or slate-gray appearance of skin and mucous membranes
  • Usually asymptomatic beyond discoloration
  • May have mild headaches, tachycardia, dyspnea 1

• Type II (severe form):

  • Similar skin discoloration plus severe neurological deficits
  • Microcephaly, dystonia, choreo-athetoid movements
  • Developmental delay, growth retardation
  • Reduced life expectancy 1

• M-hemoglobins (Hemoglobin M variants):

  • Autosomal dominant inheritance
  • Caused by mutations in α, β, or γ globin genes
  • MetHb levels 12.5-25%
  • Known as "Kochikuro" (black mouth) in Japan 1

Acquired Causes

• Medication exposure: Local anesthetics, antibiotics, nitrates
• Chemical exposure: Nitrites, aniline dyes
• Well water contamination with nitrates 1

Cyanosis

Cyanosis appears as bluish discoloration due to increased deoxygenated hemoglobin:

• Central cyanosis: Affects skin and mucous membranes due to systemic arterial desaturation

  • Cardiopulmonary disorders
  • Congenital heart disease
  • Severe pulmonary disease 5, 6

• Peripheral cyanosis: Affects extremities due to reduced peripheral blood flow

  • Cold exposure
  • Peripheral vascular disease
  • Shock states 5

Acrocyanosis

• Persistent deep blue discoloration of extremities (hands and feet)
• Due to chronic vasospasm of small cutaneous arteries and arterioles
• Can be primary or secondary to:
  • Psychiatric disorders
  • Neurologic conditions
  • Autoimmune diseases
  • Infections
  • Metabolic disorders 2

Central Venous Stenosis/Occlusion

• Causes blue or purple skin discoloration
• Often associated with:
  • Swelling of extremities, head, neck, or trunk
  • Venous collaterals on chest and neck
  • Often related to previous central venous catheterization
  • May be seen in dialysis patients with arteriovenous fistulas 1

Drug-Induced Causes

Photosensitivity Reactions

• Amiodarone: Causes photosensitivity in >50% of patients with distinctive blue-grey pigmentation
• Thiazide diuretics: Can trigger various photosensitive eruptions
• Other cardiovascular medications:
  • ACE inhibitors (ramipril, enalapril)
  • ARBs (candesartan, losartan, valsartan)
  • Dronedarone 1

Direct Pigmentation

• Minocycline: Blue-grey hyperpigmentation
• Chloroquine/hydroxychloroquine: Blue-grey discoloration
• Psychotropic medications: Phenothiazines causing slate-grey pigmentation 3

Metal Deposition

• Argyria: Grey-blue discoloration from chronic silver exposure/ingestion

  • Often from colloidal silver supplements
  • Permanent skin discoloration 7

• Chrysiasis: Blue-grey pigmentation from gold therapy

• Iron overload: Grey-brown discoloration in hemochromatosis 4

Diagnostic Approach

1. Assess distribution and pattern:

   • Generalized vs. localized
   • Mucous membrane involvement (suggests central process)
   • Extremity involvement only (suggests peripheral process)

2. Check for associated symptoms:

   • Respiratory distress, headache, fatigue (methemoglobinemia)
   • Swelling, pain (venous stenosis)
   • Photosensitivity (drug reactions)

3. Laboratory testing:

   • MetHb levels by co-oximetry (normal <1.5%)
   • Arterial blood gas analysis
   • Complete blood count

4. Special considerations:

   • Cyanosis can mask underlying anemia 5
   • Icterus (jaundice) can interfere with assessment of skin color 5

Clinical Pearls

• Blue discoloration that does not improve with oxygen therapy suggests methemoglobinemia 1
• Dennie-Morgan lines and allergic shiners can present as blue-grey periorbital discoloration but are related to allergic conditions 1
• Patients with both anemia and cyanosis may have complex clinical presentations that require careful assessment 5
• In methemoglobinemia, nasal polyps will not shrink with topical vasoconstrictors, unlike edematous mucosa 1

Remember that by the time blue discoloration is visible, oxygen saturation may already be dangerously low in cases of true cyanosis 6.