Disseminated Coccidioidomycosis with Pericarditis

can result from either slowing of the atrial rate, a decrease in the atrioventricular block, or both. The primary mechanism of quinidine-induced venbicular acceleration is the slowing of the atrial rate, but there is some evidence that a vagolytic effect on the atrioventricular node may also be partially responsible. I,! The present report demonstrates that the same acceleration of the ventricles can be produced by administration of lidocaine and ajmaline, and that therapy with lidocaine may be capable of enhancing atriovenbicular conduction even when the atrioventricular node is presumably protected by digitalis. Marriott and Bieza2 have reported a case of atrial flutter in which the ventricular rate accelerated from 165 to 265 beats per minute following administration of lidocaine, and similar cases have also been reported.' In our 6rst patient, bursts of ventricular activity at 200 beats per minute also appeared with a decrease in atrial rate from 236 to 200 impulses per minute. Rosen et al3 observed shortening of the P-His interval in four of ten patients after administration of lidocaine. The effects of lidocaine therapy on atrioventricular nodal fibers with a toxic reaction to digitalis have not been studied in detail and certainly merit further attention in the light of our experience with patient 1. Therapy with lidocaine is capable of improving atrioventricular conduction even in patients receiving digitalis,5 and our case suggests a similar effect in digitalis-induced Paroxysmal atrial tachycardia with 2: 1 block. The bursts of rapid ventricular rate in the 6rst patient became more frequent and finally changed to a 8118tained ventricular rate of 150 beats per minute under the influence of ajmaline. In the second patient, acceleration occurred just a few moments after administration of ajmaline. Ajmaline shares several properties with quinidine in its effects on cardiac fibers.e, T It decreases the maximum rate of depolarization and the velocity of conduction in Purkinje's fibers,8 and Wellens and Durrer" observed prolongation of the His-ventricle interval by ajmaline therapy in man. On the other band, as with quinidine and procaine amide hydrochloride,f.U administration of ajmaline does not always lengthen the effective refractory period of the atrioventricular node. 9 It, thus, is predictable that ajmaline therapy, by slowing the velocity of conduction and the rate in the atrium without simultaneously increasing the effective refractory period of the atrioventricular node, can produce the same paradoxic acceleration of the ventricles as quinidine and lidocaine. We concur with others 2,. that lidocaine therapy should be used for the treatment of ventricular premature beats in the presence of supraventricular tachyarrhythmias with atrioventricular block only if absolutely necessary. Our experience dictates the same caution with regard to ajmaline. The acceleration of the ventricular rate as seen here is potentially disastrous and requires prompt treatment. Administration of digitalis takes a minimum of ten minutes to be effective, or it may be contraindicated, as in case 1. Beta-adrenergic blockers mayor may not be effective. It is. therefore, of interest to note that verapamil therapy seems to be rapidly eHec-

CHEST, 71: 4, APRIL, 1977

tive. Administration of verapamil rapidly increases the effective refractory period of the abioventricular node and slows conduction of all atrial impulses through the atrioventricular node.!' Verapamil essentially fulfills the function in the atrioventricular node that is required of digitalis glycosides, acts more promptly, and is not contraindicated in the presence of digitalis intoxication.

ltEFERENCES 1 BeDet S: Clinical Disorders of the Heart Beat. Philadelphia, Lea and Febiger, 1971 2 Marriott HIL. Bieza CF: Alarming venbicular acceleration after lidocaine administration. Chest 61:682-683, 1972 3 Rosen KM, Lau SH, Weiss MB, et al: The effect of lidocaine on abioventricular and iDtraveDbicular conduction in man. Am J Cardiol25:1-5, 1970 4 Adamson AIt. SpradcJen FHN: Abial flutter with bJodc: Contraindication to use of lignocaine. Br Med J 2:223, 1968 5 Hayes JG. Ettinger E, Wanat FE, et al: Evaluation of lidocaine in the ba.tment of venbicular arrhythmia. Circulation 36(supp12) :137. 1967 6 Szelteres L. Papp JG: AntiarThythmic compounds. Prog Drug Res 12:293-369, 1968 7 Trautwein W: Generation and conduction of impulses in the heart as affected by drugs. Pharmacol Rev 15:277332, 1963 8 Pillat B. Hefstracber P: Electrophysiologische Untersuchungen uber die WirItung von Ajma)ine auf Reizleitungsfasern. Naunyn Schmiedebergs Arch Pbannaco Exp Pathol246:375.1964 9 WeDens HII. Durrer D: Effect of procaine amide. quinidine and ajmaline in the WoJff-Parkinson-White syndrome. Cireulation 50: 114-120. 1974 10 WaIJaoe AG, Cline RE. Sealey WC, et at: Electrophysiologic effects of quinidine: Studies using chronically implanted electrodes in awake dogs with and without cardiac denervation. Cire Res 19:960-969. 1966 11 Rosen Mit. Wit AL. Hoffman BF: Electrophysiology and pharmacology of cardiac arrhythmias: 6. Cardiac effects of verapamil. Am Heart J 89:665-673,1975

Disseminated Coccidioidomycosis with Pericarditis· Successful Treatment with Amphotericin B IlI'JanttJ K. Chowdhury, M.D., F.C.C.P.,oo and Mohammad A. Habiln:.adeh, M.D.t

Pericarditis with eftasioD can occur • • c:omplicatioD of disseminated coccidioidomycosis. 1af0l'lUti0B on mllll8lemeDt of this ConditiOD is very KaDty In the mediad Btenture. ODe case Is described in detaIL Early ........ and appropriate "enpy wIda amplaoteridD B ave been eat. . . . . . . keys to 88UeII In treatiIII ..... coDdidoa.

°From the Veterans Administration Hospital, Phoenix, Ariz. o °Chief, Pulmonary Disease Section. tchief, Cardiovascular Section. Reprint requests: Dr. Chowdhury, VA Hospital, Phoenix 85012

DISS£_MATED COCCIDIOIDOMYCOSIS WITH PERICARDms 533

M

ost of th e literature on coccid io id a l per ic ard itis a n ted a te the u se of a m p h otericin B, the standard antifungal agent against C occidioid es immitis . A case of acu te diss eminated cocci d io id omyc os is with p ericardia! involvement is p resented in this report. Prompt diagnosis of dissemination and p eric ardial in volvement and appropriate t herapy w ith amphot e ri c in B are d es cribed. C AS E REPORT

A 27-year-old wh ite man was admitted to the Phoenix Vet erans Administration Ho spital on F eb 24, 1975 in a moribund state wi th a six-week hi story of fev er, productive cou gh , and intermittent whee zing. The patient had newly arrived in Phoenix in June 1974 from an are a nonendemic for co ccidioid om ycosis. Ph ysical examinat ion rev ealed a ver y ill and pale you ng man wi th inspiratory and expiratory wheez e, right supraclavicular adenopathy, and a cutaneous lesion on the left for earm. Scrapings from the cutaneous lesion grew C immiiis by March 5, 1975. A chest x-ray film sh ow ed cons ide rab le mediastinal and left hil ar adenop ath y . Spinal fluid sh owe d normal values on chemistry stu d ies and a negative com p lem ent -fixat ion test for cocci di oid al infection. A skin test w ith coccid ioid in at a dilution of 1 :100 w as p ositive, wi th a 10-mm induration. Because d isseminat ed coc cidioidomycos is w as suspe cted, treatment w ith am p h ote ricin B was st arte d immediately after th e p at ient's admission to th e hospital. A dosage of 50 mg of amphoterici n B three times a wee k was the maximal amount that the patient could tolerate with ou t significant side effects. The rapy with aspirin, diphenhydramine ( Benad ry l ) , and intrave nous ad mi nistrat ion of h ydrocortison e ( 15 m g ) we re used to all eviate dis comfort during th erapy with amphoteri cin B. The complem ent-fixation tite r was stro ngly p ositive in a 1:512 dilution . P eri cardial efIus ion was suspe cte d on March 24, 1975 from th e evide nce of a che st x-ray film ( F ig 1 ) and from an echocard iog ram that revealed anterior and p oste rior ec ho -free sp a ces. During diagno sti c p eri cardiocentesis, 200 ml of ambercolore d fluid was removed. Th e fluid sho wed th e following va lues ; white blood cell cou nt, 50,0001 cu m m ; lymphocytes, 99 p er cent; protein level, 6.9 gm /l OO ml, and glucose le vel, 66 mgllOO ml. Ex am ina tion of th e fluid by a technique u sin g a mi cropore filter , as we ll as b y ce ll blocks and sm ear, failed

FIGUnE 1. C he st x-ray film ( Marc h 24, 197.5 ) shows enlar ged card iac silho ue tte and mediast inal adenopathy.

534 CHOWDHURY, HABIBZADEH

FIGUnE 2. Ech ocardiogram ( Ap ril 1976 ). Sustained small separation between pos terior ep icard iu m (Ep) an d p eri ca rdium with both ec ho es sho w ing virt u ally equal motion is cons istent with thickened visce ral and pa rie tal pericardium. IVS , Interventricular septum; Endo, end ocard iu m; and PP , parieta l pericardiu m . to show any C im m itis. T he re h ad been no evi dence of cardiac tam p onade, and the patient's symptoms h ad remained unchang ed. By Aug 29 , 1975, th e patient wa s asymptomatic and therapy w ith amphotericin B was terminated af te r a total course of 3,575 mg. Mediastinal a nd h ilar ade nop athy, a positive sp u tu m culture for C immitis, and a high complement-fixation titer wer e still present. Since Sept 8, 1975, the patient has remained at full-tim e work as manager of a ca fete ria and store . Cont inue d improvem ent of th e medi astinal and hilar adenop ath y, a decrease in the complement-fixati on tit er to 1 :4, and sp u tu m conversion to a negati ve result fo r C immitis have been ob ser ved. An ec h ocard iogra m obtained 13 mo nths after th e onset of pericardial effusion was consistent with mild pericardial thickeni ng, wi thout ev ide nce of cons tr ictive per icarditis (Fig 2). Ref er ence is made to Horowitz and associates! in the inte rpretation of th e echocardiogram . A che st x-ray film at this time showed a normal cardiac silhouette ( F ig 3) . D ISCUSSION

Most c ase s of c occ id io id a l p e ric arditis h a ve b e en re-

F IGUnE 3. Chest x-ray film ( Ap ril 13 , 1976 ) sho w s normal card iac silhouette. Me d iast ina l and left hil ar a de nop athy ar e still evident.

CHEST, 7l: 4, APRIL, 1977

ported prior to the era of amphotericin B. Forbus and Bestebreurtje" reported seven cases of pericarditis due to C immitis among 50 autopsied cases of disseminated coccidioidomycosis. Pericarditis resulted from emption of a superficially situated granulomatous lesion located in and just beneath the pericardium. Pericardial effusion and also fibrous adhesive pericarditis were observed in the series. In addition to being a disseminated lesion, pericarditis can also occur by direct extension from the pleura or an adjacent mediastinal lymph node. 8 Chapman and Kaplan! reported three cases of pericarditis in an autopsy series of 22 cases of coccidioidomycosis. The pericarditis was symptomatic in all three cases. One of three cases of coccidioidal pericarditis described by Larson and Scherb- died in "congestive heart failure." Chronic adhesive pericarditis with granuloma in the pericardium showing spherule formation was recognized at autopsy. In a necropsy series of 142 cases of fatal coccidioidomycosis, Huntington and others ll found 12 cases where the heart was involved. Fibrogranulomatous pericarditis, miliary granulomas, and abscesses of the cardiac muscle were observed. The patient described in this report was given amphotericin B in a routine manner. Local instillation of amphotericin B into the pericardial sac was not used. Diagnostic pericardiocentesis, a close watch for cardiac tamponade during the early stages of the pericarditis, and subsequent followup to exclude the possibility of constrictive pericarditis were employed. Whether the intravenous administration of hydrocortisone (15 mg), which was used with each 5O-mg dose of amphotericin B, had any influence on the course of the pericarditis or the prevention of constriction would be impossible to judge. ACKNOWLEDGMENTS: We wish to thank Mr. D. E. Deuel, Chief, Medical Media Production Service, for the photographic illustrations and Miss Marilyn Handley for secretarial support.

REFERENCES 1 Horowitz MS, Schultz CSt Stinson EB, et al: Sensitivity and specificity of echocardiographic diagnosis of pericardial effusion. Circulation 50:239-247. 1974 2 Forbus WD. Bestebreurtje AM: Coccidioidomycosis: A study of 95 cases of the disseminated type with special reference to the pathogenesis of the disease. Mwt Surg 99:653. 1946 3 Chapman MG, Kaplan L: Cardiac involvement in coccidioidomycosis. Am J Med 23:87, 1957 4 Larson R, Scherb RE: Coccidioidal pericarditis. Circulation 7 :211, 1953 5 Huntington RW Jr, Waldman WJ. Sargent JA, et al: Pathological and clinical observations on 142 cases of fatal coccidioidomycosis with necropsy. In Ajello L (ed): Pr0eeedings of the Second Coccidioidomycosis Symposium. Phoenix, Ariz, University of Arizona Press, 1965, pp 143167,1965

CHEST, 71: 4, APRil, 1977

Alphal-Antitrypsin Deficiency with DiHuse Bronchiedasis and Cirrhosis of the Liver· John H. Sea", M.D., F.C.CP.; Claw L. Anderson, M.D., F.C.C.P.; Patil S. SIaora1cM, M.D., F.C.C.P.; tmd Aleumdet- StDt>rides, M.D.

1be medical IitenItare lias empllasized repe8tedly the association of G.t--titrypsia deficiellCY with ,...claar emphysema _d cirrIIoIII of the lYer. Pre reports ave IiDked IJroDCh1ec:t8s1s wida (11-autitr' de8cieDcy. TIae prese" C8Ie confirms this .-oclation and adds the presellCe of 8ft hepllfic .........., dl8ndelildc 01 (1tautilrypsla deadeney to complete tile syndrome. The ,.. tleat'l pIIeDotype was foad to be IIJ>artes. It . . been saaated that patieDCs wltIa dUfuse broDCh1ec:t8s1s silo... be screeBed for (1t-autib',psba deldeney. We would add tbat a complete _ e a t of hepatic faRctioD, iDcIadIDg liver biopsy, should be carried oat ill tlaOle iDdlvidaals with red1Ieed levels of G.1-antl1rypsiD.

is a A lpha1-antitrypsin serum, and its deficIency

inhibit~ in the associated WIth pulmonary emphysema,1-8 hepatic abnormalities in infants and children, ~ as well as adults,7-8 and bronchiectasts.'.• In recent years, cirrhosis of the liver associated with emphysema and (11-antitrypsin deficiency has been recognized in children'" and adults. l1- 13 A case c4 (1t-antitrypsin deficiency in association with cirrhosis of the liver and severe bronchiectasis in an adult has come under our observation and is reported herein. ~jor

~ease. 15

CASE REPoRT A 53-year-old white man was admitted to the hospital with complaints of increasing headache, fatigue, somnolence, dyspnea on exertion, and productive cough. He gave a past history of repeated respiratory infections since the age of 13. The patient had smoked cigarettes for 30 pack-years but had stopped smoking at the age of 45. He had consumed alcoholic beverages in moderate amounts for 20 years. There was no history of blood transfusion. Physical examination revealed a dyspneic man with clubbing, cyanosis, and pedal edema. The pulse rate was 96 beats per minute and regular, the respiration rate was 3O/minute, and the blood pressure was 150/70 mm Hg. Expiratory wheezes and "crackling" rales were heard over the lower third of both lungs. There was a loud second sound at the pulmonic area. The liver was palpable on deep inspiration; the spleen was not palpable. Chest x-ray 6lms showed evidence of a diffuse. moderately dense reticular pattern throughout the lung fields, with honeycombing (Fig 1). Saccular and cylindric bronchiectatic changes were present in both lungs on bronchograms obtained in 1972 (Fig 2). The results of a complete blood cell count and routine urinalysis were normal Arterial blood gas levels (patient breathing room air) were as foI·From the Division of Pulmonary Medicine. Western Pennsylvania Hospital, Pittsburgh. Reprint requests: Dr. Scott. 4815 Liberty Avenue, Pittsburgh 15224

ALPHAt-AIITITRYPSIN DEFICIENCY 535