Scholarly article on topic 'Coccidioidal pericarditis: a case presentation and review of the literature'

Coccidioidal pericarditis: a case presentation and review of the literature Academic research paper on "Clinical medicine"

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{Coccidioidomycosis / Pericarditis / Tamponade / Constriction / Cardiomegaly}

Abstract of research paper on Clinical medicine, author of scientific article — Edward L. Arsura, Ravi K. Bobba, Chakradhar M. Reddy

Summary Background: Pericardial involvement with Coccidioides immitis is an infrequent occurrence with a relatively unfavorable prognosis. Methods: A case of coccidioidal pericarditis is presented along with a review of the medical literature on coccidioidal pericarditis to give the clinician a better understanding of the various presentations, complications and outcomes of this disease. Medline (National Library of Medicine, Bethesda) was electronically searched covering the years 1966–2003 using search words coccidioidomycosis and pericarditis. Results: Sixteen patients were identified from the literature review and one new patient was added. All the patients were males with a mean age of 37.5 years. Chest pain, dyspnea and cough were the most common presenting symptoms. Five patients had evidence of pericardial tamponade, pulsus paradoxus was noted in three patients and three patients presented with pericardial constriction. One patient had Kussmaul's sign, one patient had pericardial frictional rub and another had pericardial knock. Cardiomegaly on chest x-ray was present in ten patients; EKG was noted to have low voltage in five and ST segment elevation in four patients. Delayed hypersensitivity to coccidioidal antigen was reported in nine patients and positive in eight patients. Complement fixation titers were positive in all 11 patients in whom it was assayed. Fifty-three percent of the patients with coccidioidal pericarditis died. Conclusion: Coccidioidal pericarditis is a rare disease entity that has a relatively unfavorable prognosis, yet many patients present with diagnostic clues to this disorder. An enhanced understanding of the clinical features of coccidioidal pericarditis may lead to improved outcomes.

Academic research paper on topic "Coccidioidal pericarditis: a case presentation and review of the literature"

International Journal of Infectious Diseases (2005) 9, 104—109

ELSEVIER

Coccidioidal pericarditis: a case presentation and review of the literature$

Edward L. Arsuraa b c *, Ravi K. Bobbab, Chakradhar M. Reddyb

aUniversity of Virginia, Charlottesville, Virginia, USA bSalem Veterans Medical Center, 1970 Roanoke Salem Boulevard, Salem, VA 24153, USA cKern Medical Center, 1830 Flower Street, Bakersfield, CA 92305, USA

Received 1 March 2004; received in revised form 27 April 2004; accepted 17 May 2004 Corresponding Editor: Michael Ellis, El Ain, UAE

Summary

Background: Pericardial involvement with Coccidioides immitis is an infrequent occurrence with a relatively unfavorable prognosis.

Methods: A case of coccidioidal pericarditis is presented along with a review of the medical literature on coccidioidal pericarditis to give the clinician a better understanding of the various presentations, complications and outcomes of this disease. Medline (National Library of Medicine, Bethesda) was electronically searched covering the years 1966—2003 using search words coccidioidomycosis and pericarditis. Results: Sixteen patients were identified from the literature review and one new patient was added. All the patients were males with a mean age of 37.5 years. Chest pain, dyspnea and cough were the most common presenting symptoms. Five patients had evidence of pericardial tamponade, pulsus paradoxus was noted in three patients and three patients presented with pericardial constriction. One patient had Kuss-maul's sign, one patient had pericardial frictional rub and another had pericardial knock. Cardiomegaly on chest x-ray was present in ten patients; EKG was noted to have low voltage in five and ST segment elevation in four patients. Delayed hyper-sensitivity to coccidioidal antigen was reported in nine patients and positive in eight patients. Complement fixation titers were positive in all 11 patients in whom it was assayed. Fifty-three percent of the patients with coccidioidal pericarditis died. Conclusion: Coccidioidal pericarditis is a rare disease entity that has a relatively unfavorable prognosis, yet many patients present with diagnostic clues to this disorder. An enhanced understanding of the clinical features of coccidioidal pericarditis may lead to improved outcomes.

# 2004 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

$ Presented at AFMR (Eastern Section) Baltimore, Maryland, March 2003. * Corresponding author. Tel.: +1 540 983 1001; fax: +1 540 983 1028. E-mail address: edward.arsura@med.va.gov (E.L. Arsura).

INTERNATIONAL SOCIETY

FOR INFECTIOUS DISEASES

http://intl.elsevierhealth.com/journals/ijid

KEYWORDS

Coccidioidomycosis;

Pericarditis;

Tamponade;

Constriction;

Cardiomegaly

1201-9712/$30.00 © 2004 International Society for Infectious Diseases. Published by Elsevier Ltd. All rights reserved. doi:10.1016/j.ijid.2004.05.006

Coccidioidal pericarditis: a case presentation and review of the literature

Introduction

Infection with the pathogenic fungus Coccidioides immitis can lead to several clinical outcomes. Sixty percent of those exposed to the organism remain asymptomatic or demonstrate symptoms so mild that medical intervention is not sought. Approximately 40% develop symptoms which are usually pulmonary and self-limited in nature. In symptomatic patients, disseminated disease may develop in up to 5%. Extrapulmonary spread of the fungus is associated with significant morbidity and occasional mortality, especially in those with factors such as an ethnic predisposition or an immunocompromised state. The most frequent sites of dissemination include lymph nodes, skin and subcutaneous tissue, meninges and bones.1

Pericardial involvement with Coccidioides immitis is an infrequent occurrence with fewer than 20 cases reported in the medical literature. Involvement of the pericardium can lead to diagnostic confusion with other disease entities that cause pericarditis and given its infrequent occurrence the diagnosis can be overlooked. In this article, a case of pericardial involvement due to Coccidioides immitis is presented along with a review of the medical literature on coccidioidal pericarditis. The clinical syndromes that may occur are highlighted, which may give the clinician a better understanding of the various presentations and complications of this disease.

In the literature review, 16 cases with pertinent clinical information were discovered.2-9,12,13 One additional case of coccidioidal pericarditis seen by the authors is added to bring the total to 17 patients. Two autopsy series10,11 with 25 cases of coccidioidal pericarditis that did not include any relevant details were also reviewed, however these studies were not incorporated in this review.

Methods

Medline (National Library of Medicine, Bethesda) was electronically searched covering the years 1966-2003 using search words coccidioidomycosis and pericarditis. Case series focusing on coccidioi-domycosis identified through Medline from 19662003 and culled cases with coccidioidal pericarditis from these series were also reviewed. To identify additional original studies, reference lists of reviewed articles dating back to 1929, the published meeting proceedings from the International Symposium on Coccidioidomycosis which meets every five years, and leading infectious diseases texts were also reviewed.

The identified patients' demographic data reviewed clinical symptoms and associated findings were tabulated. Laboratory findings, EKG, chest x-ray, fluid analysis, therapy provided and clinical outcome were the noted parameters.

Case report

A 34-year-old Hispanic male presented in July 1996 after two months of fever, night sweats and a 20-pound weight loss. There was a non-productive cough. Chest x-ray revealed an anterior mediastinal mass, which on fine needle aspiration was positive for acid-fast bacilli. Skin tests for tuberculosis and coccidioidomycosis were both negative. The patient was started on isoniazid, rifampin and pyrazinamide and cultures were subsequently positive for Mycobacterium tuberculosis. He was found to have human immunodeficiency virus (HIV) infection and was started on antiretroviral therapy and trimethoprim/sulfamethoxazole. The CD4 count was 30/ mm3. Symptoms improved with weight gain and cessation of cough. In December 1996, the cough reappeared and a sputum analysis was positive for Coccidioides immitis. A complement fixation titer for Coccidioides immitis was positive at a dilution of 1:32. An evaluation for fungal dissemination including a lumbar puncture and bone scan were negative. Chest x-ray showed improvement in the mediastinal mass. Fluconazole at a dose of 400 mg daily was started.

Three months later a 3 x 5 cm left supraclavicular mass was noted, which on fine needle aspirate yielded both Mycobacterium tuberculosis and Coccidioides immitis. His medications were continued and there was a 50% reduction in the size of the supraclavicular mass although constitutional symptoms recurred along with a five-pound weight loss. Within two months a right 4 cm, right axillary lymph node was noted. A fine needle aspirate revealed spherules with endosporulation and culture of the lymph node was positive for Coccidioides immitis. The dose of fluconazole was increased to 800 mg/ day.

Despite this therapeutic change additional lymph node enlargement occurred. The complement fixation titer for coccidioidomycosis was 1:256. He completed 12 months of antituberculous therapy and was continued on fluconazole 400 mg daily.

Seventeen months after his initial presentation, he was admitted for worsening fever, weight loss, fatigue and anterior chest pain. Chest x-ray on admission revealed an increase in the cardiac silhouette consistent with pericardial effusion. An echocardiogram revealed a large pericardial

effusion without evidence of pericardial tamponade. Analysis of pericardial fluid revealed a total white count of 3200 cells/mm3 with 91% lymphocytes and 9% neutrophils. Pericardial fluid culture was positive for Coccidioides immitis. Acid fast stain and culture for Mycobacterium tuberculosis were negative. Treatment with amphotericin B was discussed, however the patient declined this option. The dose of fluconazole was increased to 1000 mg daily. The patient's fever, chills, fatigue, and anorexia improved transiently, however within several weeks of discharge they recurred with consequent, progressive decline. At this point, the patient elected to have only comfort measures instituted and he died within several weeks.

Results

Age, sex and race

The present review describes 17 patients with coccidioidal pericarditis. All patients were male with a mean age 37.5 years (range 20—78 years). Ethnicity was described in 13 patients: four Caucasian, three African-American, three Hispanic, two Filipino and one Pacific Islander.

Clinical presentation

Chest pain was the most common symptom occurring in 12 patients. Dyspnea was noted in 11 patients, cough in six patients and orthopnea in four patients (Table 1).

Five patients showed evidence of pericardial tamponade with pulsus paradoxus in three patients. Equalization of pressures was noted in two patients (one patient had pericardial tamponade and the other had pericardial constriction). Four patients had pericardial constriction. Two of these patients had progression of pericarditis with tamponade to pericardial constriction. At times it was difficult to discern whether tamponade or constriction was the most prominent component and in one case there was clear evidence of effusive-constrictive physiology. One patient had Kussmaul's sign. One patient had a pericardial friction rub and another had a pericardial knock. Two patients had physical findings of right-sided volume overload.

Seven patients had disseminated disease, with cutaneous spread or extrathoracic lymph node involvement being the most common sites of dissemination. Three patients had widespread dissemination. The underlying myocardium was involved in four patients (autopsy report).

Radiology, laboratory and microbiology

Chest x-ray findings were notable for cardiomegaly in ten patients and mediastinal adenopathy in four patients.

Electrocardiograms were performed in 12 patients. Five patients had low voltage, four patients had ST elevation, four patients had Twave inversions and two patients had non-specific ST-T wave changes.

In four patients, the diagnosis of coccidioidal pericarditis was made based on clinical findings with laboratory, x-ray and EKG support. The diagnosis was confirmed by culture of pericardial fluid in three patients and pericardial biopsy in four patients. In six patients, the diagnosis was established at autopsy.

Delayed hypersensitivity to coccidioidal antigen was reported in nine patients. It was positive in eight patients and negative in one (this patient was HIV positive and profoundly immunocompromised). In one patient, who developed disseminated disease, the skin test went from positive to negative. The complement fixation titer was positive in all 11 patients in whom it was assayed.

Pericardial fluid was obtained in nine patients and analysed in three patients, with lymphocytic predominance in two (WBC 50 x 109/L, 99% lymphocytes and 3.2 x 109/L, 91% lymphocytes) and 45% lymphocytes (WBC 4.7 x 109/L) in the third patient.

Treatment and outcome

Of the nine patients treated with antifungal agents, seven received amphotericin B, and two received fluconazole.

Nine patients died; six of these patients had disseminated disease. One patient died of tamponade, one patient died from pericardial constriction and one patient died in the first post-pericardiect-omy day. Eight patients recovered and three of these patients required pericardiectomy.

Discussion

Coccidioidal pericarditis is an infrequent complication of infection with Coccidioides immitis, a fungus endemic in desert regions of the southwestern United States, Central and South America. The pericardium is the primary cardiac structure that is involved by C. immitis with neither the myocardium nor endocardium being recognized clinically, although there have been reported autopsy

Table 1 Clinical, laboratory characteristics, treatments and outcomes of patients with coccidioidal pericarditis.

Patient Symptoms Clinical features Lab Treatment Outcome Diagnosis

1 Chest pain, dyspnea, NA +CST None 2 recurrences, died Autopsy

orthopnea

2 Chest pain, dyspnea, Subcutaneous abscess +CST None Died Autopsy

orthopnea

3 Cough, dyspnea, Papular skin lesions NA None Died Autopsy

orthopnea

4 Cough Right heart failure, +CST None Died Autopsy

constriction

5 Chest pain NA +CST, +CFT None 4 recurrences, recovered Clinical

6 Chest pain, cough, Pericardial friction rub +CST, +CFT None Recovered Clinical

dyspnea

7 Chest pain, dyspnea, Tamponade +CFT 1:128 Amphotericin B Recurrent tamponade, Pericardial fluid

orthopnea died analysis

8 Chest pain, dyspnea, Tamponade, +CST, + CFT 1:32 Amphotericin B Recovered Culture of

pulsus paradoxus pericardial fluid

9 Chest pain Pulsus paradoxus, +CST, +CFT 1:128 Amphotericin B Pericardiectomy recovered, Pathologic study

right heart failure, of pericardium

pericardial knock,

tamponade, constriction,

adenopathy

10 Cough Skin lesions, adenopathy +CST, +CFT 1:512 Amphotericin B Recovered Clinical

11 Chest pain, dyspnea, NA NA, +CFT 1:128 Fluconazole 1 recurrence, recovered Clinical

12 Cough, dyspnea Pulsus paradoxus, NA None Pericardiectomy, died Autopsy

equalization of pressures,

constriction

13* Chest pain Adenopathy -CST+CFT 1:256 Fluconazole 1 recurrence, died Culture of pericardial fll lirl fluid

14 Chest pain, dyspnea, Kussmaul sign, tamponade, +CFT 1:8 Amphotericin B Recovered, Pathologic study of

equalization of pressures, pericardiectomy pericardium

constriction

15 Chest pain, cough, NA NA Amphotericin B Pericardiectomy, died Pathologic study of

dyspnea, facial plethora pericardium

16 Dyspnea, weight loss NA +CFT 1:2 Amphotericin B & Complete Pericardiectomy Pathologic study of

Fluconazole pericardium

17 Dyspnea and chest pain NA +CFT 1:16 None Complete pericardiectomy Autopsy

CST: coccidioidal skin test; CFT: complement fixation titer; NA: not applicable; Patient numbers and references: (1,2,3)4 (4,5,6)7 (7,8)3 (9)9 (10)5 (11)2 (12)8 (14)6 (15)12 (16,17)13.

observations.10,11,14 Clinical pericardial involvement is detailed in only 17 patients.2-9,12,13 The presentation can be acute, progress rapidly to effu-sive-constrictive physiology or the presentation can be that of a chronic constrictive process.5,6

Relapsing pericarditis is seen in some patients. The initial symptom complex for patients with coccidioidal pericarditis is usually nondescript, and does not differ significantly from pulmonary coccidioidomycosis, with chest pain and pulmonary symptoms predominating. However, certain features of coccidioidal pericarditis such as orthop-nea, pulsus paradoxus, Kussmaul's sign, pericardial friction rub, and a pericardial knock can help the clinician arrive at the correct diagnosis. Four patients had a history of coccidioidomycosis treated with antifungals and then developed symptomatic pericardial disease.

The organism may arrive at the pericardium by one of several routes. In many of the patients, the exact mechanism is unclear. For example, eight patients had pulmonary infiltrates and three patients had pleural effusions, which could be the source of contiguous spread. Mediastinal lymphade-nopathy in four patients could be the source of lymphatic spread. Hematogenous spreading to the pericardium is a possibility in those with disseminated disease.

The most sensitive finding in coccidioidal pericarditis was the presence of cardiomegaly on chest x-ray that was found in nine patients. EKG abnormalities were present in all patients who had the study performed. Four patients had EKG changes that were highly suggestive of pericardial fluid (low voltage) and four patients had EKG abnormalities indicative of pericarditis (diffuse ST segment elevation).

Eight of nine patients had positive delayed hyper-sensitivity to coccidioidal antigen and serum complement fixation titer was positive in all patients in whom it was measured. These findings in the appropriate clinical context of patients living in or visiting an endemic area would assist with the diagnosis. Pericardial fluid, when analysed, revealed a lym-phocytic predominance in two patients and 45% lymphocytes in the third.

Only two patients, including the additional case, were immunocompromised (HIV infection and non-Hodgkin's lymphoma).

Seventy-five percent of the reported cases occurred in individuals with an ethnic/racial predisposition.

The morbidity and mortality of coccidioidal pericarditis is significant. Fifty-three percent of the patients with coccidioidal pericarditis died. The majority of those who died had disseminated dis-

ease, which has an intrinsically worse prognosis. Four patients who died were diagnosed before the advent of effective antifungal therapy. Autopsy series of disseminated coccidioidomycosis identified pericardial infection in 5-14%.9

Pericardiectomy for coccidioidal pericarditis has been successful in young patients.6 The goal is complete resection, freeing the heart from the constrictive process. Pericardiectomy was necessary in seven patients and was planned in one patient who died. Nine patients had pericardial constriction. Pericardiocentesis was carried out in four patients and one patient required pericardiot-omy.

An interesting and striking finding in coccidioidal pericarditis is that all reported cases were males. A male predominance is noted in other forms of coccidioidomycosis but not in such a marked fashion as seen in coccidioidal pericarditis. There is no obvious explanation for this gender preference, however occupational exposure or a hormonal influence on the growth of C. immitis has been postulated.

Coccidioidal pericarditis is a rare disease entity that has a relatively unfavorable prognosis. Many patients present with clues to the presence of this disorder and it is hoped that an enhanced understanding of coccidioidal pericarditis will lead to improved outcomes.

References

1. Stevens DA. Coccidioidomycosis. N Engl J Med 1995; 332:1077—82.

2. Amundson DE. Perplexing pericarditis caused by coccidioidomycosis. South Med J 1993;86:694-6.

3. Bayer AS, Yoshikawa TT, Galpin JE, Guze BL. Unusual syndromes of coccidioidomycosis: diagnostic and therapeutic considerations. Medicine 1976;55:131-52.

4. Chapman MG, Kaplan L. Cardiac involvement in Coccidioidomycosis. JAMA 1957;23:87-98.

5. Chowdhury JK, Habibzadeh MA. Disseminated coccidioidomycosis with pericarditis. Chest 1977;71:533-5.

6. Faul JL, Hoang K, Schmoker J, Vagelos RH, Berry GJ. Con-strictive pericarditis due to coccidioidomycosis. Ann Thorac Surg 1999;68:1407-9.

7. Larson R, Scherb RE. Coccidioidal pericarditis. Circulation 1953;7:211-7.

8. Oudiz R, Mahaisavariya P, Peng SK, Shane-Yospur L, Smith C, Baumgartner F, Shapiro S. Disseminated coccidioidomycosis with rapid progression to effusive constrictive pericarditis. J Am Soc Echocard 1995;8:947-52.

9. Schwartz EL, Waldmann EB, Payne RM, Goldfarb D, Kinard SA. Coccidioidal pericarditis. Chest 1976;70:670-2.

10. Evans N, Ball HA. Coccidioidal granuloma; analysis of 50 cases. JAMA 1929;93:1881-5.

11. Forbus WD, Bestebreurtje AM. Coccidioidomycosis. A study of 95 cases of the disseminated type with special reference

Coccidioidal pericarditis: a case presentation and review of the literature

to the pathogenesis of the disease. Mil Surg 1946;99:653— 719.

12. Aguilar JA, Summerson C, Granda MC, Jiminez C, de La Torre S. Pericarditis caused by Coccidioidomycosis. Report of a Case. Arch Cardiol Mex 2001;71:313—8.

13. Visbal AL, DeValeria PA, Blair JE, ZarkaMA, Lanza LA. Coccidioidal pericarditis: implications of surgical treatment in the elderly. Ann Thorac Surg 2003;75:1328-30.

14. Lee V. Coccidiodomycosis: in the western flying training command. Calif West Med 1944;61:133.

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