Diagnostic Approach to Blue Tongue

Causes and Clinical Presentation

• A blue tongue is most commonly caused by methemoglobinemia, which presents as blue discoloration of the tongue, lips, nose, cheeks, and buccal mucosa that does not improve with supplemental oxygen, according to the American Journal of Hematology 1
• Methemoglobinemia can be congenital or acquired, and typically causes methemoglobin levels >10% when blue discoloration is present, as noted by the American Journal of Hematology 1
• The European Heart Journal recommends considering cyanotic heart disease with right-to-left shunting as a cause of systemic hypoxemia in patients with blue tongue 3

Diagnostic Workup

• The American Journal of Hematology recommends measuring methemoglobin levels using blood gas measurement by co-oximetry as the key diagnostic test 2
• The American Journal of Hematology also recommends assessing oxygen saturation using pulse oximetry, noting that conventional pulse oximetry may be unreliable in methemoglobinemia 1, 2
• The European Heart Journal suggests evaluating for hypoxemia that does not improve with oxygen supplementation, and obtaining a complete blood count to assess for polycythemia and rule out hematologic malignancies 3, 5

Laboratory Tests and Imaging

• The American Journal of Hematology recommends measuring cytochrome b5 reductase enzymatic activity if congenital methemoglobinemia is suspected, and genetic testing for CYB5R3 mutations (for Type I congenital methemoglobinemia) or CYB5A mutations (for Type II) 1, 2
• The European Heart Journal suggests echocardiography if cyanotic heart disease is suspected, and cardiac MRI or CT for further evaluation of complex congenital heart defects 3
• The Circulation journal recommends evaluating liver enzymes, serum creatinine, and albumin to assess organ function 5, 6

Clinical Approach and Management

• The American Journal of Hematology recommends considering treatment with methylene blue if symptomatic methemoglobinemia is present, and identifying and removing any causative agents 1, 2
• The European Heart Journal suggests considering cardiac evaluation for cyanotic heart disease if methemoglobin levels are normal 3
• The American Journal of Hematology notes that patients with chronic cyanosis may develop secondary erythrocytosis, hyperuricemia, and renal dysfunction, and recommends avoiding routine phlebotomies in these patients 5