Sore throat, fever and neutropenia in a patient on clozapine

A 34-year-old man with treatment-resistant schizophrenia was admitted to the ward with sore throat and fever. He had been started on clozapine eight weeks earlier, with the dose titrated over 14 days to 300 mg once daily. He had also been taking valproate sodium 500 mg twice daily for six months for mood stabilisation. Five days before admission, he had developed a dry cough and was started on amoxicillin 500 mg three times daily by the community team for a suspected chest infection. On the morning of admission, he reported a sore throat and fever of 38.7°C. There were no other localising symptoms. He had not experienced any rigors, but felt generally weak.

On examination, he was flushed, with a temperature of 38.4°C, heart rate 96/minute, blood pressure 114/68 mmHg. The pharynx was erythematous without exudate. Chest examination was clear, and no lymphadenopathy was found. The rest of the examination was unremarkable.

Laboratory results on admission showed a total white cell count of 1.8 ×10^9/L, with an absolute neutrophil count of 0.2 ×10^9/L. Haemoglobin was 13.5 g/dL and platelet count was 180 ×10^9/L. C-reactive protein was 89 mg/L. The blood film showed no blasts, and the appearance was consistent with agranulocytosis.

In view of the profound neutropenia, clozapine was stopped immediately. Amoxicillin was continued to treat the suspected infection. The patient was isolated and placed on neutropenic precautions. Over the following five days, the neutrophil count recovered progressively: day 2, 0.6; day 3, 1.1; day 5, 2.4 ×10^9/L. The fever resolved by day 2, and the sore throat improved by day 3. No rechallenge was attempted.