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June 15, 2005June 15, 2005

Ann ChenAnn Chen

History of Present IllnessHistory of Present Illness

31 yo male, residing at West Seattle Psychiatric 31 yo male, residing at West Seattle Psychiatric Hospital, brought to HMC for fevers, chills, and Hospital, brought to HMC for fevers, chills, and dyspnea.dyspnea.

Father notes that he seems to be more agitated Father notes that he seems to be more agitated then at baseline.then at baseline.

Poor historian. SOB for 1-4 days. Associated Poor historian. SOB for 1-4 days. Associated with chest pain. Does not appear to have cough with chest pain. Does not appear to have cough or sputum production.or sputum production.

ROS positive for HA, whole-body myalgia, and ROS positive for HA, whole-body myalgia, and diarrhea. Denies any weight loss, nightsweats.diarrhea. Denies any weight loss, nightsweats.

Past Medical HistoryPast Medical History

PMH:PMH: SchizophreniaSchizophrenia

SHx:SHx: + tobacco, 2-3ppd since 18yrs old+ tobacco, 2-3ppd since 18yrs old Past EtOHPast EtOH Denies IVDUDenies IVDU

Meds:Meds: Metoprolol (recently added)Metoprolol (recently added) Risperidone Risperidone Clozaril (dose increased recently)Clozaril (dose increased recently) CogentinCogentin DepakoteDepakote RanitidineRanitidine

More HistoryMore History

No travels in past 10 yearsNo travels in past 10 years Has one dog at home, no birdsHas one dog at home, no birds Had negative PPD when he started Had negative PPD when he started

residing at the psych facilityresiding at the psych facility Family history with “some kind of cancer”, Family history with “some kind of cancer”,

otherwise non-contributoryotherwise non-contributory

Physical ExamPhysical Exam T=40.6, BP=125/67, HR=130s, RR=40s to 50s, O2 T=40.6, BP=125/67, HR=130s, RR=40s to 50s, O2

sat=99% on 100NRBsat=99% on 100NRB AAOx3, mildly diaphoreticAAOx3, mildly diaphoretic HEENT: PERRL, EOMI, no JVD, oral mucosa without HEENT: PERRL, EOMI, no JVD, oral mucosa without

lesions, no cervical LANlesions, no cervical LAN Lungs: using accessory muscles, decreased breath Lungs: using accessory muscles, decreased breath

sounds at bases, no crackles or wheezessounds at bases, no crackles or wheezes CV: tachycardic, regular, good peripheral pulsesCV: tachycardic, regular, good peripheral pulses Abd: obese, nontender, no reboundAbd: obese, nontender, no rebound LE: trace edema LE: trace edema Skin: no rashSkin: no rash Neuro: CN intact, nonfocalNeuro: CN intact, nonfocal

LabsLabs

WBC=11.8, Hct=38, Plt=165WBC=11.8, Hct=38, Plt=165 Diff: neutrophils 70%, eosinophils 10%Diff: neutrophils 70%, eosinophils 10% Chem 7 normalChem 7 normal LFTs normal, amylase and lipase normalLFTs normal, amylase and lipase normal ABG: 7.47/31/108 on 6L O2 via NCABG: 7.47/31/108 on 6L O2 via NC Troponin=0.52, CK=316Troponin=0.52, CK=316 BNP = 1337BNP = 1337 EKG: sinus tach, otherwise normalEKG: sinus tach, otherwise normal

Pleural EffusionPleural Effusion

Pleural effusion: eosinophilicPleural effusion: eosinophilic Gram stain and bacterial cultures negativeGram stain and bacterial cultures negative AFB negativeAFB negative Fungal, viral negativeFungal, viral negative

ECHOECHO

EF of 40%EF of 40% LV with normal wall thickness and size but LV with normal wall thickness and size but

with mild global hypokinesiswith mild global hypokinesis RV normal size and functionRV normal size and function Mild MR, otherwise no valvular Mild MR, otherwise no valvular

abnormalitiesabnormalities Small pericardial effusionSmall pericardial effusion

More LabsMore Labs

PCR for enteroviruses and adenovirus PCR for enteroviruses and adenovirus negativenegative

Resp FA: negative for influenza A & B, Resp FA: negative for influenza A & B, parainfluenza, RSV, adenovirusparainfluenza, RSV, adenovirus

HIV negativeHIV negative CMV IgG positive, CMV antigenemia CMV IgG positive, CMV antigenemia

negativenegative ESR=50, CRP=306ESR=50, CRP=306 ANA, ds-DNA, ANCA negativeANA, ds-DNA, ANCA negative

Stool StudiesStool Studies

Strongyloides antibody negativeStrongyloides antibody negative Stool cultures negative for O&PStool cultures negative for O&P C.diff toxin A & B negativeC.diff toxin A & B negative

Clozapine HypersensitivityClozapine Hypersensitivity Reported cases of clozapine causing:Reported cases of clozapine causing:

Pleural effusionPleural effusion PericarditisPericarditis Pericardial effusion, tamponadePericardial effusion, tamponade MyocarditisMyocarditis CardiomyopathyCardiomyopathy ArrhythmiasArrhythmias Sudden cardiac deathSudden cardiac death

Other side effects:Other side effects: AgranulocytosisAgranulocytosis SeizuresSeizures

TachycardiaTachycardia SedationSedation Weight gainWeight gain HypersalivationHypersalivation

Clozapine-Induced Clozapine-Induced Polyserositis & MyocarditisPolyserositis & Myocarditis

Onset of symptoms described as early as 1 week Onset of symptoms described as early as 1 week to as late as 7 years after starting clozapineto as late as 7 years after starting clozapine

Patient age ranged from 25 to 66 years oldPatient age ranged from 25 to 66 years old Dose ranged from 100mg to 750mg daily Dose ranged from 100mg to 750mg daily Patients presents with the usual clinical signs and Patients presents with the usual clinical signs and

symptoms of pleural effusions, pericarditis, and symptoms of pleural effusions, pericarditis, and myocarditismyocarditis

Peripheral eosinophiliaPeripheral eosinophilia Pathology clozapine-induced myocarditis showed Pathology clozapine-induced myocarditis showed

eosinophilic infiltration of myocardiumeosinophilic infiltration of myocardium

TreatmentTreatment

Resolution of symptoms with stopping clozapine Resolution of symptoms with stopping clozapine Steroids???Steroids???

Proposed mechanism: Clozapine stimulates release Proposed mechanism: Clozapine stimulates release of TNF and other cytokinesof TNF and other cytokines

Thus, steroids have been triedThus, steroids have been tried One case of biopsy-proven myocarditis that improved One case of biopsy-proven myocarditis that improved

with 8-day course of “low-dose corticosteroids”with 8-day course of “low-dose corticosteroids” Jury is still out…Jury is still out…

ReferencesReferences Pieroni M, Cavallaro R, Chimenti C, Smeraldi E, Frustaci Pieroni M, Cavallaro R, Chimenti C, Smeraldi E, Frustaci

A. Clozapine-induced hypersensitivity myocarditis. Chest A. Clozapine-induced hypersensitivity myocarditis. Chest 2004;126:1703-1705.2004;126:1703-1705.

Wehmeier PM, Heiser P, Remschmidt H. Myocarditis, Wehmeier PM, Heiser P, Remschmidt H. Myocarditis, pericarditis and cardiomyopathy in patients treated with pericarditis and cardiomyopathy in patients treated with clozapine. Journal of Clinical Pharmacy and clozapine. Journal of Clinical Pharmacy and Therapeutics 2005;30:91-96.Therapeutics 2005;30:91-96.

Murko A, Clarke S, Black DW. Clozapine and pericarditis Murko A, Clarke S, Black DW. Clozapine and pericarditis with pericardial effusion. Am J of Psychiatry with pericardial effusion. Am J of Psychiatry 2002;159:494.2002;159:494.

Fineschi V, Neri M, Riezzo I, Turillazzi E. Sudden cardiac Fineschi V, Neri M, Riezzo I, Turillazzi E. Sudden cardiac death due to hypersensitivity myocarditis during death due to hypersensitivity myocarditis during clozapine treatment. Int J Legal Med 2004;118:307-309.clozapine treatment. Int J Legal Med 2004;118:307-309.