Dapsone

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An event is serious (based on the ICH definition) when the patient outcome is:

• * death

• * life-threatening

• * hospitalisation

• * disability

• * congenital anomaly

• * other medically important event

A 34-year-old woman developed methaemoglobinaemia, intravascular haemolysis and acute on chronic anaemia during prophylactic treatment with dapsone [duration of treatment to reaction onsets not stated].

The woman, who had a history of lupus nephritis, anaemia of chronic kidney disease and systemic lupus erythematosus, presented with a 1-week history of progressive fatigue dyspnoea on exertion and palpitations. She had received atovaquone and prednisone followed by primaquine and clindamycin two months prior for Pneumocystis jiroveci pneumonia. Since then, she had been receiving prophylactic dapsone [dosage and route not stated] along with prednisone and mycophenolate mofetil. At admission, her lab tests were as follows: Hb 6.7 g/dL, haptoglobin 19 mg/dL, WBC 3.62 K/uL, ferritin 721 ng/mL, bicarbonate 20 mEq/L, potassium 6.2 mEq/L and anion gap 9. Her creatinine level was 2.13 mg/dL, which was consistent with the baseline kidney function. She was hospitalised for suspected COVID-19 and acute on chronic anaemia with a probable haemolysis.

The woman's dapsone therapy was stopped, and she was treated with multiple packed RBC transfusions. Her COVID-19 test came negative ruling out the infection. During the next 36h, she experienced dyspnoea with increasing palpitations. She also developed headache, distal paresthesias and dizziness. Despite normal oxygen saturations on pulse oximetry, her lips were progressively cyanotic. Methaemoglobin level was found to be 28.5%. A diagnosis of symptomatic dapsone-induced methaemoglobinaemia was made, which was likely exacerbated due to the anaemia. She was treated with cimetidine and methylthioninium chloride [methylene blue]. A significant improvement was noted in her symptoms within and hour. She remained asymptomatic during the next few days. Her methemoglobin levels returned between ~10−15%. Cimetidine was continued until her methaemoglobin level was under 10%.