Mycoplasma-Associated Pericarditis

Case Report Mycoplasma-Associated Pericarditis RAMI S. FARRAJ, M.D.,* ROBERT B. MCCULLY, M.B.,CH.B., JAE K. OH, M.D., AND THOMAS F. SMITH, PH.D. munofluorescence antibody titers were consistent with recent M. pneumoniae infection, and antibiotic therapy resulted in rapid and complete resolution of the patient's symptoms. This treatable entity may be underrecognized and can now be diagnosed with sensitive serologic testing. (Mayo Clin Proc 1997; 72:33-36)

Mycoplasma pneumoniae-associated pericarditis may result in pronounced morbidity unless appropriate therapy is administered. In this report, we describe a patient who had recurrent episodes of chest pain, intermittent constitutional symptoms, and, eventually, cardiac tamponade due to pericarditis despite treatment with nonsteroidal anti-inflammatory drugs. Im-

cardia and low voltage in the precordial leads. Chest roentgenography disclosed small bilateral pleural effusions without pulmonary infiltrates, and echocardiography revealed a small circumferential pericardial effusion (Fig. 1 A and 2 A). Blood, urine, and throat bacterial cultures were negative. Indomethacin therapy, 50 mg three times a day, was initiated. The pain diminished, and the patient was dismissed from the hospital; the diagnosis was acute pleuropericarditis. The patient continued to have a low-grade fever and decreased exercise tolerance. During the next 3 weeks, a dry cough, dyspnea on minimal exertion, orthopnea, and paroxysmal nocturnal dyspnea developed. After being readmitted to the hospital, she was found to have a regular pulse rate of 90 beats/min, blood pressure of 140/70 mm Hg, and an increased jugular venous pressure. On auscultation, fine late inspiratory crackles were detected in the lower zones of both lung fields. Chest roentgenography revealed cardiomegaly and pulmonary venous congestion. No pulmonary infiltrates were noted. Over several hours, the patient's blood pressure gradually decreased to 80/50 mm Hg. She experienced tachycardia (110 beats/min), and her jugular venous pressure remained increased. An echocardiogram (Fig. 1 B) revealed a moderate circumferential pericardial effusion with Doppler evidence of cardiac tamponade (Fig. 2 B). The patient underwent echocardiographic-guided pericardiocentesis, and 150 mL of serosanguineous fluid was removed. Her blood pressure increased within minutes after the procedure. The pericardial catheter was left in place for 3 days to facilitate intermittent drainage. The dyspnea resolved. Cytologic, Gram stain, mycobacterial, aerobic, and anaerobic bacterial cultures of the pericardial fluid yielded negative results. Indomethacin therapy was resumed, and she was dismissed from the hospital. The patient continued to have symptoms of generalized weakness, arthralgia, myalgia, and mild dyspnea. One

REPORT OF CASE A 57-year-old previously healthy woman came to the emergency department because of severe, stabbing interscapular and chest pain (based on a scale of 0 to 10, severity was 8) of several hours' duration. The pain extended into her left arm and was associated with dyspnea, fatigue, nausea, and diaphoresis. On physical examination of the patient, her pulse rate was 90 beats/min and regular, and her blood pressure was 110/70 mm Hg in both arms; no audible murmur, rub, or gallop was detected. Further inpatient assessment included serial electrocardiograms and cardiac enzymes, a chest roentgenogram, and arterial blood gas studies. Results of these studies and a radioactive ventilation-perfusion lung scan, Doppler ultrasound study of the lower extremities, and n-dimer test were normal. The patient underwent exercise echocardiography. Left ventricular systolic function was normal, and there were no regional wall motion abnormalities at rest or immediately after exercise. No pericardial effusion was noted. The patient's pain decreased with use of ibuprofen, and she was dismissed; the diagnosis was indeterminate chest pain. After 5 months of intermittent fatigue, the patient was hospitalized because of another episode of retrosternal chest pain, low-grade fever (38.2°C), and tachycardia (110 beats/ min). Findings on the rest of her physical examination were unremarkable. An electrocardiogram revealed sinus tachy-

From the Department of Internal Medicine (R.S.F.), Division of Cardiovascular Diseases and Internal Medicine (R.B.M., J.K.a.), and Division of Clinical Microbiology (T.F.S.), Mayo Clinic Rochester, Rochester, Minnesota. *Current address: King Hussein Medical Center, Amman, Jordan. Address reprint requests to Dr. R. B. McCully, Division of Cardiovascular Diseases, Mayo Clinic Rochester, 200 First Street SW, Rochester, MN 55905. Mayo Clin Proc 1997; 72:33-36

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Fig.!. Two-dimen sional echocardiograms (apical four-chamber view). A, Small pericardial effusion (PE) (arrow). B, PE (arrow) was larger 3 weeks later when patient had cardiac tamponade . LA = left atrium; LV = left ventricle; RA = right atrium; RV = right ventricle.

month later at outpatient follow-up, she was noted to have normocytic anemia; her hemoglobin concentration was 10.5 g/dl., and the erythrocyte sedimentation rate was 95 mm in 1 hour . She also had an unexplained eosinophilia ( 12%), and her total leukocyte count was 11.7 X 109/L. Serologic tests for antibodies to Mycopla sma pn eumoniae were performed as part of a further evaluation for possible systemic dise ase. IgG (l: 160) and IgM (1:20) titers , obtained with immunofluorescence testing, were consistent with recent infection with M. pneumoniae. The patient was treated with azithromycin because she remained symptomatic and was intolerant of erythromycin and tetracycline therapy. A dose of 500 mg on the first day and 250 mg daily for the next 9 days was used. Within 3 day s after initiation of therapy, the patient had complete resolution of her dyspnea and sys temic symptoms, and she resumed normal activity. Findings on an echocardiogram obtained 3 week s after antibiotic therapy had been initiated were normal. Her pericardial effusion had not recurred. Three months after therapy, the patient was still asymptomatic; laboratory studies revealed a hemoglobin concentration of 12.8 g/dL, an erythrocyte sedimentation rate of2 3 mm in 1 hour, and a leukocyte count of7.6 X 109/L (eosinophils, 1.5%). Convalescent IgG ( 1:40) and IgM (less than 1:10) titers of M . pneumoniae antibodies were con sistent with a past infection. DISCUSSION In our patient, pericarditis was diagnosed only after the recurrence of symptoms following her initial diagnosis of indeterminate chest pain. Before her third and last hospitalization, dyspnea was the predominant symptom . Although

signs of cardiac tamponade developed while she was in the hospital, her clinical picture on admission was that of congestive heart failure with an increased jugular venous pressure , bibasilar pulmonary crackles on physical examination, and pulmonary venous congestion on che st roentgenography. Pure cardiac tamponade rarel y, if ever, cau ses frank pulmonary edema.' Studies in canine models, however , have shown that progressive pericardial effusion and tamponade lead to accumulation of extravascular fluid in the lungs, resulting in lung stiffening and decreased static lung compliance.' This situation increases the work of breathing and ma y explain the sensation of dy spnea. Our patient's initi al clinical improvement after pericardiocentesis supports the theory that her symptoms and signs were due to the hemodynamic effe cts of card iac tamponade. Myocarditis or myopericarditis might have othe rwise explained the clin ical picture; however, an echocardiogram demonstrated normal left ventricular sys tolic function. Radiologic studies showed no evidence of superimposed pneumonia. M . pn eumoniae is usuall y con sidered in the differential diagnosis of atypical pneumonia, especially in young healthy adults . Thi s organism can , however, have extrapulmonary rnanifestation s.v' Mycoplasma-associated pericarditis is a rare example of invasive Mycoplasma- associated systemic disease. We are aware of only 11 previously reported cases of pericarditis asso ciated with M . pneumoniae .: " Our case report may be the first to describe untreated M. pneumoniae as the cause of ongoing pericarditis. In a study of 57 pati ent s who underwent surgical treatment because of large peri cardial effusions," pericardial fluid and tissue samples were studied cytologically, and cultures

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Fig. 2. Pulsed wave Doppler signal (at leaflet tips) of mitral inflow recorded with respirometry (Resp) done at same time two-dimensional echocardiographic images (Fig. 1) were obtained. A, Stable diastolic signal of early (E) and late (A) filling throughout respiratory cycle. B, Attenuated early filling velocity (small arrowhead) immediately after onset of inspiration (lnsp) that increases (large arrowhead) after onset of expiration (Exp). This pronounced respiratory variation in inflow signal is characteristic of cardiac tamponade. 1

for aerobic and anaerobic bacteria, fungi, mycobacteria, Mycoplasma, and viruses were done. A diagnosis was made in 53 patients (93%). Malignant disease was the most common finding. Eight patients had an infectious cause, including M. pneumoniae, cytomegalovirus, herpes simplex virus, Mycobacterium avium-intracellulare, and Mycobacterium chelonei. Detection of Mycoplasma organisms in pericardial fluid and tissue provides the most direct and definitive way of establishing the diagnosis of infectious pericarditis; however, up to 1 month may be necessary for these fastidious organisms to grow in culture, and thus this method is usually unhelpful for the clinical management of patients. Moreover, the successful growth of M. pneumoniae in culture from patients with serologic evidence of infection by complement fixation test was only 64%.13 The recent availability of sensitive and specific serologic tests for M. pneumoniae'" may allow for the evaluation of small pericardial effusions not considered large enough to require pericardiocentesis.

The inexpensive and widely available complement fixation test for antibodies to M. pneumoniae has a sensitivity and specificity of 90% and 94%, respectively," although the specificity was questionable in patients with extrapulmonary manifestations. IS Studies that used the indirect immunofluorescence test have reported sensitivities and specificities greater than 95%.16-18 In our patient, the presence of a high IgM antibody titer with the immunofluorescence test during acute illness and its return to normal during convalescence supported the diagnosis of M. pneumoniae infection." Her dramatic clinical response to antibiotics, however, provides the most compelling support for the diagnosis. Frequently, physicians fail to consider the possibility of Mycoplasma-associated pericarditis. M. pneumoniae infections should be suspected in patients with or without pulmonary infiltrates who have systemic symptoms such as arthralgia, myalgia, or fever and evidence of other organ involvement. Initial studies may also show normocytic anemia and eosinophilia. Cold agglutinins are present in only 30 to 50% of M. pneumoniae infections but are among the

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first markers to change during the acute phase of infection. They are nonspecific, however, especially in low titers," and are not recommended for the laboratory diagnosis of M. pneumoniae infections. Throat cultures are positive in 77% of serologically positive cases' but may also be positive in 4.6 to 13.5% of healthy persons." Hence, if Mycoplasma infection is suspected, specific serologic testing for M. pneumoniae should be done. Our case demonstrates that ongoing systemic infection with M. pneumoniae can result in pronounced morbidity and persist until appropriate treatment is initiated.

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10. 11. 12. 13.

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