Clozapine-induced pneumonitis mimicking an atypical pneumonia

Clozapine is an antipsychotic used for treatment-resistant schizophrenia with a significant side effect profile, including agranulocytosis, myocarditis and fever. Clozapine-induced fever often occurs in the first 2 weeks of treatment and settle after a few days. We report a case of a woman in her mid-30s who developed fever and infective symptoms suggestive of an atypical pneumonia while on clozapine titration. She was on clozapine for 16 days before developing high-grade fever, dry cough, diarrhoea, headache and photophobia with a very high CRP. We performed an extensive infection workup that returned negative results except for bilateral upper lobe ground glass changes of the lungs on CT. Despite antibiotic therapy, which would cover an atypical pneumonia, her CRP remained elevated and her fever persisted. Focus was directed to clozapine-induced pneumonitis as the cause for her symptoms. Her antibiotics were ceased, and clozapine was downtitrated. With the adjustment of her clozapine dose, her fevers and associated symptoms resolved, and CRP downtrended. Her fevers did not return when clozapine was uptitrated in the community subsequently. Clozapine-induced fever or other immune-allergic reactions should be systematically considered when patients develop fever during the initiation phase of clozapine therapy. Ruling out infective causes is desirable prior to attributing fevers to clozapine especially when they are accompanied by infective symptoms and high inflammatory markers. Careful downtitration of clozapine should be considered rather than abrupt cessation in managing clozapine-induced fevers and subsequent slow uptitration could be considered.