Severe Psychotic Disorder and Agranulocytosis – A Therapeutic Dilemma

Schizophrenia is a severe mental disorder leading to chronic disability, poor social functioning and an increased risk of harm to self [6] and others [8] . The most important treatment is pharmacotherapy with diff erent classes of antipsychotics. However, these substances bear considerable risks of side eff ects. The most dangerous is agranulocytosis (absolute neutrophil count ANC < 100 / μ L) with mortality rates between 5 and 10 % . All antipsychotics can cause agranulocytosis, the highest risk is known for clozapine [4] . For all neuroleptics, the use is restricted in case of mild neutropenia (ANC < 1 500 / μ L) and contraindicated in case of moderate (ANC < 1 000 / μ L) and severe neutropenia (ANC < 500 / μ L). Several reports describe continuation of clozapine treatment despite neutropenia with co-administration of granulopoesisstimulating factors [3] or rechallenge with clozapine following neutropenia during previous therapy [2] . However, administration or continuation of neuroleptics in patients with continuous severe neutropenia has never been reported so far. We describe a case in which an urgent need for antipsychotic therapy was obvious against the background of a critical clinical situation with pre-existing severe neutropenia. In January 2007, a 39-year-old man was referred to our hospital after an attempted suicide. He had wounded himself in a forest with a carpet cutter at both back of the feet and the left forearm imitating the cicatrices of Jesus Christ. A chronic paranoid schizophrenia had been diagnosed about three years before. In 2002, he quit his job, was unemployed from then on and lived with his parents. Neutropenia was known since 2004 with a leukocyte count of about 2 500 / μ L. Recurrent hematological diagnostic investigations including bone marrow histology, immunophenotyping and cytogenetic analysis did not reveal any hematological disease. No further decline occurred under treatment with haloperidol but with amisulpride and risperidone. Having experienced severe extrapyramidal side eff ects under haloperidol, fi nally the patient had been discharged without neuroleptic treatment after his last admission. Actually, he experienced auditory hallucinations and religious delusions. We administered lorazepam to suppress suicidal ideas. Initially, no neuroleptics were given because of the known neutropenia. The lowest spontaneous leukocyte count was 1 400 / μ L, the lowest neutrophil count 234 / μ L, thus meeting the clinical criteria of agranulocytosis. Two administrations of granulocyte-colony stimulating factor G-CSF yielded high but not sustained leukocyte counts indicating an intact bone marrow. In the meantime, the patient wounded himself again and presented ongoing suicidal ideation based on psychotic ideas. Thus, neuroleptic treatment was strongly indicated ( ● ▶ Fig. 1 ). Further immunohematological work-up revealed the presence of strong anti-neutrophil autoantibodies, consistent with a diagnosis of autoimmune neutropenia ( ● ▶ Fig. 2 ). Secondary autoimmune neutropenia due to other reasons could be excluded. Primary autoimmune neutropenia is a well-described disorder in chil-