Probable clozapine-induced parenchymal lung disease and perimyocarditis: a case report

Abstract

BackgroundClozapine is the archetypical atypical antipsychotic, its primary indication being treatment resistant schizophrenia. Severe side effects caused by clozapine, including leukopenia, agranulocytosis, and myocarditis, are well known. A rarely described side effect is concurrent perimyocarditis and parenchymal lung disease.Case presentationA previously physically healthy 23-year-old male Caucasian that suffered from schizophrenia presented with flu-like symptoms 1 week after starting clozapine treatment. Treatment with clozapine was discontinued. He developed respiratory distress. Investigations showed significant parenchymal infiltration in both of the lungs, pericardial fluid, and heart failure. He initially received treatment for suspected malignant neuroleptic syndrome and later for suspected infection, but these tentative diagnoses were not confirmed. The patient’s condition gradually improved. In retrospect, clozapine-induced parenchymal lung disease and perimyocarditis were deemed the most probable causes.ConclusionsConcurrent perimyocarditis and parenchymal lung disease are rare side effects of clozapine. Clozapine-induced disease in general is considered an exclusion diagnosis. Lacking a verifiable diagnosis when suspecting a side effect of clozapine, clinicians might treat the most likely and serious condition presenting and consider discontinuing clozapine until the diagnostic uncertainty is reasonably resolved.

Clozapine-Induced Pneumonitis: A Case Report

“…Drug-induced pneumonitis is a very rare adverse reaction of clozapine. To our knowledge, seven cases have been reported in the literature previously ( 4 – 10 ), but likely more cases have occurred unreported or undiagnosed. The clinical approach to clozapine-induced pneumonitis is a diagnostic challenge as neutropenia with increased risk of infection is far more commonly associated with clozapine than non-infectious lung injury ( 2 ).…”

“…It is essential to rule out infectious processes of lung injury as untreated these conditions may be life-threatening. Every prior case published that was reviewed of clozapine-induced pneumonitis was associated with pulmonary infiltrates on either chest x-ray and/or computed tomography (CT), while auscultation findings, symptom severity, oxygen saturation, and pulmonary function tests varied from case to case ( 4 – 10 ). Additionally, the diagnosis of clozapine-induced pneumonitis requires a temporal relationship between the onset of symptoms and the administration of clozapine, as well as resolution of symptoms and pulmonary infiltrates after clozapine is withdrawn.…”

“…However, in one similar case of clozapine-induced lung disease Arias et al did perform a bronchoalveolar lavage which showed predominance of lymphocytes and a lung biopsy which revealed mild inflammation without granulomas ( 6 ). Hypersensitivity reactions have also been associated with clozapine ( 13 , 14 ), however, specific laboratory makers such as eosinophilia have not been consistent in the presentation of clozapine-induced pneumonitis ( 4 – 10 ). There have been cases of clozapine associated eosinophilia causing multisystem organ failure, including pneumonitis, which may also present similarly to sepsis ( 10 , 14 ).…”

“…There is less published information on the rarer adverse reactions of clozapine, especially lung disease. To our knowledge, seven case reports of non-infectious and non-allergic clozapine-induced lung disease have been reported in the literature ( 4 – 10 ). Clinical assessment for a drug-induced pneumonitis is challenging, as it is a diagnosis of exclusion and its clinical presentation may imitate sepsis.…”

A Very Rare Adverse Effect Of Clozapine, Clozapine-Induced Interstitial Lung Disease: Case Report And Literature Review

“…The diagnosis relies upon: a) an association between exposure and the subsequent development of symptoms; b) lung infiltrates; c) the exclusion of other causes, and d) symptom resolution once the agent is withdrawn (3). To date, there have been only a few case reports in the literature (2,(4)(5)(6)(7). Here, we present a case of clozapine-induced interstitial lung disease, and discuss it both in terms of clinical experience and its relationship to extant medical literature.…”