Eosinophilia, Pleural Effusion, Hepatitis, and Jaundice Occurring Early in Clozapine Treatment
Ms. A, a 47-year old woman with a 15-year history of schizophrenia, was hospitalized after noncompliance with antipsychotic medications, which resulted in decompensation characterized by aggressive behavior, auditory hallucinations and delusions. All laboratory tests performed on admission, including complete blood cell count (CBC), serum electrolytes, urinalysis, and liver function tests (LFTs), were within normal limits. Hepatitis serology revealed that the hepatitis B surface (HBs) antibody was positive and that the HBs antigen was negative. Ms. A was a non-smoker and non-drinker with no history of substance misuse and no significant medical history.\nDue to poor responses to previous antipsychotic treatments, the patient was started on clozapine with the dose titrated from 12.5 mg/day to 300 mg/day during a 4-week period. During this period the patient had no other medications.\nThe weekly checks of the CBC showed gradual increases in the eosinophil count following the beginning of clozapine treatment. The eosinophil count was 0.9% (57/mm3) before clozapine use, 1.7% (142/mm3) at day 8, 2.8% (248/mm3) at day 15, and 5.0% (416/mm3) at day 22. On day 29, the total leukocyte count increased to 10,910/mm3, and the eosinophilia reached 23.6% (2,575/mm3). Ms. A did not have any symptoms.\nOn day 35, the patient complained of general myalgia and 37.5℃ fever. Both leukocytosis (16,500/mm3) and eosinophilia (28.9%, 4,769/mm3) were aggravated. A chest X-ray revealed some amount of right side pleural effusion. The pleural effusion was considered to be the cause of the fever and leukocytosis, and conservative management of oral antibiotics was provided. Because clozapine was effective in managing the psychotic symptoms, it was maintained at the reduced dosage of 100 mg/day. On day 42, the total leukocyte count was normalized, at 9,230/mm3 but the eosinophil count had increased to 54.2% (5,003/mm3). She showed an intermittent 37.7℃ fever, but general myalgia had disappeared. On day 44, a repeat chest X-ray revealed that the pleural effusion had nearly disappeared, and the fever had subsided. The total leukocyte and eosinophil count decreased to 8,350/mm3 and 40.1% (3,348/mm3), respectively.\nOn day 48, the patient suddenly became jaundiced, and she was transferred to the department of internal medicine at a general hospital. The total leukocyte count was 3,600/mm3 with 12.9% (464/mm3) eosinophil. The LFTs were notable for the following abnormalities: alanine transaminase (ALT) 254 IU/L (range, 4-43), aspartate transaminase (AST) 277 IU/L (range, 7-38), r-glutamyl-transferase (GGT) 573 U/L (range, 8-48), total bilirubin 6.0 mg/dl (range, 0.2-1.2), and direct bilirubin 3.5 mg/dl (range, 0.1-0.4). Abdominal computed tomography showed hepatopathy by acute hepatitis. The urinalysis showed urobilinogen 2+ (range, trace). The patient retrospectively reported that her urine color had changed to red during the previous 2 weeks.\nAfter 5 days without clozapine, the LFTs improved, showing an ALT level of 22 IU/L, an AST level of 37 IU/L, a GGT level of 46 U/L, a total bilirubin of 0.6 mg/dl, and a direct bilirubin of 0.2 mg/dl. The total leukocyte count was 4,200/mm3 with 10.5% (441/mm3) eosinophil. Ms. A was readmitted to our hospital after 1 week without clozapine for treatment of psychotic symptoms. The total leukocyte count was 4,400/mm3 with 3.4% (150/mm3) eosinophil on the day of readmission. There were no recurrences of LFT or CBC abnormalities during following treatment with olanzapine and haloperidol.