A 23-year-old man comes to the emergency department due to sudden-onset fatigue and dark urine. The patient was recently diagnosed with dermatitis herpetiformis. He began treatment with dapsone and a gluten-free diet 3 days ago. This morning, the patient felt weak and had difficulty getting out of bed. His urine also appeared dark. Temperature is 36.8 C (98.2 F), blood pressure is 130/76 mm Hg, pulse is 88/min, and respirations are 14/min. The patient appears tired. Examination shows scleral icterus and pale lips. There is a papular rash along the scalp, elbows, and knees with overlying excoriation. Laboratory evaluation reveals the following: Which of the following is the most likely mechanism for this patient's urinary findings?

Question

A 23-year-old man comes to the emergency department due to sudden-onset fatigue and dark urine.  The patient was recently diagnosed with dermatitis herpetiformis.  He began treatment with dapsone and a gluten-free diet 3 days ago.  This morning, the patient felt weak and had difficulty getting out of bed.  His urine also appeared dark.  Temperature is 36.8 C (98.2 F), blood pressure is 130/76 mm Hg, pulse is 88/min, and respirations are 14/min.  The patient appears tired.  Examination shows scleral icterus and pale lips.  There is a papular rash along the scalp, elbows, and knees with overlying excoriation.  Laboratory evaluation reveals the following:  Which of the following is the most likely mechanism for this patient's urinary findings?

Quizplus · Accepted Answer

Explanation: This patient developed hemolytic anemia (eg, low hemoglobin, reticulocytosis, icterus) after taking dapsone, likely indicating underlying glucose-6-phosphate dehydrogenase (G6PD) deficiency. In this condition, erythrocytes are unable to generate sufficient NADPH to counter oxidative injury (eg, superoxide anions) from certain medications (eg, dapsone, trimethoprim-sulfamethoxazole, primaquine), infections, or foods (eg, fava beans). This results in periods of hemolytic anemia, whereby lysed erythrocytes release heme into the circulation, leading to: Hyperbilirubinemia - heme is catabolized to bilirubin, which causes scleral icterus and jaundice Hemoglobinuria - heme is excreted in the kidneys, which causes dark-colored urine and a false-positive urine dipstick for blood (the heme in hemoglobin causes a positive urine dipstick test, but no erythrocytes are seen on urine microscopy) (Choice A) Antibody-mediated hemolysis is seen with warm or cold agglutinin disease. Certain medications can also cause immune-mediated hemolysis, but most cases are linked to cephalosporins, penicillins, and nonsteroidal antiinflammatory drugs. In contrast, dapsone is classically linked with G6PD exacerbations. agglutinin disease (Choice B) Complement activation contributes to hemolytic uremic syndrome, which is associated with microangiopathic hemolytic anemia, thrombocytopenia, and acute renal injury. Urinalysis typically shows hematuria and proteinuria. This patient's platelets are normal and no red blood cells are present in the urine. (Choice C) Immune complex deposition causes membranous glomerulonephritis, leading to hematuria with dysmorphic red cells on urinalysis. Most cases are caused by chronic infection (eg, hepatitis B or C), rheumatic disease (eg, systemic lupus erythematosus), or monoclonal gammopathy (eg, multiple myeloma). (Choice D) Interstitial leukocyte infiltration is seen in acute interstitial nephritis, which can be associated with antibiotics (eg, trimethoprim-sulfamethoxazole). However, urinalysis typically shows erythrocytes, leukocytes, and white cell casts. Furthermore, patients frequently have rash, fever, and/or peripheral eosinophilia. Educational objective: Glucose-6-phosphate dehydrogenase deficiency causes hemolytic anemia due to oxidative injury to red blood cells. Hemolytic episodes can be precipitated by infection or medications, especially dapsone, antimalarials, and nitrofurantoin.

A 23-Year-Old Man Comes to the Emergency Department Due to Sudden-Onset