Delayed Onset Adult Respiratory Distress Syndrome in Babesiosis

myocardium or pericardia! effusions may suggest neoplastic complications. Gallium scintigraphy also may be a useful adjunctive radiographic tool. As suggested by others, when unexplained pericardia! effusions are detected in the symptomatic patient, attempts should be made to obtain fluid or tissue for culture and histologic preparation. 16 When cardiac tamponade is present, drainage procedures should be performed for diagnostic and therapeutic purposes. The importance of establishing a timely diagnosis is highlighted by occasional favorable responses to multiagent chemotherapy. REFERENCES

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Beral V, Peterman T, Berkelman R, Jaffe H. AIDS associated non-Hodgkin's lymphoma. Lancet 1991; 337:805-09 Biggar RJ , Rabkin CS. The epidemiology of acquired immunodeficiency syndrome-related lymphomas. Curr Opin Oncol 1992; 4:883-93 Gail MH, Pluda JM, Rabkin CS, Biggar RJ, Goedert JJ, Horm JW, et al. Projections of the incidence of non-Hodgkin's lymphoma related to acquired immunodeficiency syndrome. J Nat! Cancer Inst 1991; 83:695-701 Pluda JM, Yarchoan R, Jaffe ES, Feuerstein IM, Solomon D, Steinberg SM, eta!. Development of non- Hodgkin's lymphoma in a cohort of patients with severe human immunodeficiency virus (HIV) infection on long-term antiretroviral therapy. Ann Intern Med 1990; 113:276 Pluda JM, Venzon D, Tosato G, Lietzau J, Shay LE, Karp JE, et a!. Factors which predict for the development of nonHodgkin's lymphoma in patients with HIV infection receiving antiretroviral therapy. Blood 1991; 78:285a Non-Hodgkin's Lymphoma Pathologic Classifications Project. National Cancer Institute sponsored study of classifications of non-Hodgkin's lymphomas: summary and description of a working formulation for clinical usage. Cancer 1982; 49:2112-35 Lukes RJ, Parker JW, Taylor CR, Tindle BH, Cramer AD, Lincoln TL. Immunologic approach to non-Hodgkin's lymphoma and related leukemias: analysis of the results of multiparameter studies of 425 cases. Semin Hematol1978; 15:322-51 Levine AM. AIDS-related lymphoma. Blood 1992; 80:8-10 Levine AM, Sullivan-Halley J, Pike MC, Rarick M Loureiro C, Bernstein-Singer M, et a!. HIV related lymphoma: prognostic factors predictive of survival. Cancer 1991; 68:2466-72 Horowitz H , Wormser G. HIV associated heart disease. The AIDS Reader 1992; May / June:99-108 Holladay AO, Siegal RJ, Schwartz D. Cardiac malignant lymphoma in acquired immunodeficiency syndrome. Cancer 1992; 70:2203-07 Gill P, Chandraratna A, Meyer P, Levine AM. Malignant lymphoma: cardiac involvement at initial presentation. J Clin Oncol1987; 5:216-24 Ziegler JL, Beckstead JA, Volberding PA, Abrams DI, Levine AM, Lukes RJ, et al. Non-Hodgkin's lymphoma in 90 homosexual men: relation to generalized lymphadenopathy and the acquired immunodeficiency syndrome. N Eng! J Med 1984; 311:565-70 Guarner J, Brynes RK, Chan WC, Birdsong G, Hertzler G. Primary non- Hodgkin 's lymphoma of the heart in two patients with the acquired immunodeficiency syndrome. Arch Pathol Lab Med 1987; 111:254-56 Constantino A, West TE, Gupta M, Loghmanee F. Primary cardiac lymphoma in a patient with acquired immunodeficiency syndrome. Cancer 1987; 60:2801-05 Goldfarb A, King CL, Rosenzweig BP, Feit F , Kamal BR, Romancik WM, et al. Cardiac lymphoma in the acquired immu-

nodeficiency syndrome. Am Heart J 1989; 118:1340-44 17 McAllister H, Feneglio J. Tumors of the cardiovascular system. Atlas of tumor pathology. Second Series. Washington DC: Armed Forces Institute of Pathology, 1978; 99-100 18 Curtsinger C, Wilson M, Yonedi K. Primary cardiac lymphoma. Cancer 1989; 64:521-25 19 ChouS, AcklesB, Gill G, PinkusN, Parkin A, HicksJD. Primary lymphomas of the heart: a case report. Cancer 1983; 52:744-47 20 Pozniak AL, Thomas RD, Hibbs CB, Lever JV. Malignant lymphoma of the heart: antemortem cytologic diagnosis. Acta Cytol 1986; 30:662-64 21 Petersen CD, Robinson W A, Kurnick JE. Involvement of the heart and pericardium in the malignant lymphomas. Am J Med Sci 1976; 272:161-65 22 Balasubramanyam A, Waxman M, Kazal HL, Lee MH. Malignant lymphoma of the heart in acquired immune deficiency syndrome. Chest 1986; 90:243-46 23 Andress JD, Polish LB, Clark DM, Hossack KF. Transvenous biopsy of a cardiac lymphoma in an AIDS patient. Am Heart J 1989; 118:421-23 24 Dalli E, Guesada J, Paya H. Cardiac involvement by nonHodgkin's lymphoma in acquired immune deficiency syndrome. Int J Cardia! 1990; 26:223-25 25 Helfand J. Cardiac tamponade as a result of American Burkitt's lymphomas of the heart and pericardium. Conn Med 1990; 54:186-89 26 Kelsey RC, Saker A, Morgan M. Cardiac lymphoma in a patient with AIDS. Ann Intern Med 1991; 115:370-71 27 Monsuez JJ, Kinney EL, Vittecoq D, Kitzis M, Rozenbaum M, d'Agay MF, eta!. Comparison among acquired immune deficiency syndrome patients with and without clinical evidence of cardiac disease. Am J Cardiol 1988; 62:1311-13 28 Reynolds M, Hecht S, Berger M, Kolokathis A, Horowitz S. Large pericardia! effusions in the acquired immune deficiency syndrome. Chest 1992; 102:1746-47 29 Lewis W. AIDS: cardiac findings from 115 autopsies. Prog Cardiovasc Dis 1989; 32:207-15 30 Silver MA, Macher MA, Reichert CM, Levens DL, Parrillo JE, Longo DL, et al. Cardiac involvement by Kaposi's sarcoma in acquired immune deficiency syndrome (AIDS). Am J Cardia! 1984; 53:983-85 31 Monsuez JJ, Kinney EL, Vittecoq D, Kitzis M, Rozenbaum W, d 'Agay MF, et al. Comparison among acquired immune deficiency syndrome patients with and without clinical evidence of cardiac disease. Am J Cardiol1988; 62:1311-13 32 Sider L, Weiss A, Smiton M, VanRoenn JM, Glasroth J. Varied appearance of AIDS related lymphoma of the chest. Radiology 1989; 171:629-32 33 Kaplan LD, Abrams DI, Feigal E, et a!. AIDS associated nonHodgkin's ly mphoma in San Francisco. JAMA 1989; 61:719-24 34 Cammarosano C, Lewis W. Cardiac lesions in acquired immune deficiency syndrome (AIDS). J Am Coli Cardia! 1985; 5:703-06

Delayed Onset Adult Respiratory Distress Syndrome in Babesiosis* Mitchell L. Horowitz, M.D.; Frank Coletta, M.D.; and Alan M. Fein, M.D., F.C.C.P. *From the Pulmonary & Critical Care Medicine Division, Winthrop- University Hospital, Mineola, NY, and State University of New York at Stony Brook. Reprint requests: Dr. Fein, Winthrop-Pulmonary Associates, PC 222 Station Plaza North, Suite 400, Mineola, NY 11501 CHEST / 106 / 4 / OCTOBER, 1994

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Reported herein is a second case of a patient who developed adult respiratory distress syndrome secondary to babesiosis. The features of acute lung injury after babesiosis will be described.

(Chest 1994; 106:1299-1301) ARDS=adult respiratory distress syndrome Key words: acute lung injury, ARDS, babesiosis

B

abesiosis is a tick-borne disease caused by an intraerythrocytic protozoan parasite, Babesia microti. 1 It is transmitted like Lyme disease, by the nymphal Ixodes dammini tick, and these two diseases may occur simultaneously.2 While babesiosis usually is asymptomatic, more severe disease can present as a multisystem illness similar to malariaa·4 Immunosuppression, advanced age, and prior splenectomy are risk factors for severe babesiosis. 5 Despite reports of severe sepsis and multiorgan dysfunction in babesiosis, respiratory involvement only rarely has been described. 1•6 •7 A review of the medical literature reveals only three patients in whom respiratory manifestations have been noted. Two patients had a cough and one patient developed adult respiratory distress syndrome (ARDS). This is in contrast to infection with Plasmodium falciparum malaria, which is frequently complicated by noncardiogenic pulmonary edema and respiratory failure.8·9 In one report, 9 of 21 patients with severe malaria required mechanical ventilation for ARDS, and one of these patients died. 8 In another series, the mortality for severe malaria was reported to be about 20 percent, and up to 80 percent with superimposed ARDSB We report a second patient who developed ARDS secondary to babesiosis. The unique features of acute lung injury following babesiosis will be described. CASE REPORT

Medical History

A 70-year-old white man presented to the emergency room with a 3-day historyof fever, shaking, chills, malaise, and a 1-day history of confusion. He had been receiving erythromycin 1 day before admission. His medical history included hypertension, mitral regurgitation, and tuberculosis which had been inactive since 1930. He had recently travelled to both Lyme, Conn, and eastern Long Island, New York, but was unaware of having been bitten by a tick. Physical Examination

His temperature was 40° C; the pulse was 104 beats per minute and regular; arterial blood pressure was 130/ 70 mm Hg; and respiratory rate was 18 breaths per minute. Lung examination revealed bibasilar rales, while examination of the heart was remarkable for a grade 2/ 6 systolic ejection murmur which was unchanged from a prior examination. No other abnormalities were noted. Abnormal laboratory value data included: Na, 116 mEq / L; blood urea nitrogen level, 23 mg / dl; WBC count, 7,600 cells/ cumm ,3 with 75 percent neutrophils, 8 percent hypersegmented neutrophils, 4 percent lymphocytes, and 1 percent eosinophils; hemoglobin level, 12.3 gm / dl; aspartate aminotransferase, 83 IU / L; alanine aminotransferase, 53 IU / L; alkaline phosphatase, 119 IU / L; gamma-glutamyl transpeptidase= 133 U / L; prothrombin time, 14.5 s; lactic dehydrogenase value, 456 IU / L; total bilirubin level, 3.4 mg/ dl. A Wright-stained peripheral blood smear 1300

FIGURE l. Babesiosis and ARDS. revealed 2 percent intraerythrocytic ringed organisms consistent with Babesia species. Atetrad was noted in the RBCs, confirming the diagnosis of babesiosis. A Lyme antibody titer by enzyme-linked immunosorbent assay, done at the time of admission, was negative. A chest roentgenogram revealed cardiomegaly and pleural thickening in the left upper lung field , which was unchanged from a previous chest x-ray film done 15 months earlier. An ECG demonstrated sinus tachycardia at 109 beats per minute. Hospital Course

Therapy with clindamycin and qumme for babesiosis was started. Tuberculosis cultures eventually proved to be negative. The hyponatremia was treated effectively with fluid restriction. The patient's fever waxed and waned during the first three hospital days, after which defervescence occurred. On hospital day 4, the patient suddenly became tachypneic with a respiratory rate reaching 40 breaths per minute. Arterial blood gas analysis revealed: pH, 7.37; PaC02, 43 mm Hg; Pa02, 36 mm Hg; and Sa0 2, 67 percent while on a 100 percent nonrebreather mask. The patient was intubated and placed on mechanical ventilation. The chest roentgenogram showed bilateral multilobar alveolar infiltrates (Fig 1). A Swan-Ganz catheter was inserted on hospital day 6 to assess the cause of the pulmonary edema. Pulmonary artery pressure was 37/ 14 mm Hg and pulmonary capillary wedge pressure was 15 mm Hg, indicating that cause of pulmonary edema was not hydrostatic. The pulmonary capillary wedge pressure remained below this level until removal of the catheter on day 10. Weaning from mechanical ventilation was begun 4 days after intubation, and the patient was extubated on the lOth day and discharged on the 20th day after admission. DISCUSSION

The patient we described developed severe hypoxic respiratory failure, diffuse infiltrates on the chest radiograph, and elevated airway pressures while being ventilated, which is consistent with ARDS as a consequence of acute babesiosis. While the patient had a history of underlying hypertension and valvular heart disease, pulmonary edema persisted for 5 days with low to normal pulmonary capillary wedge pressures. There were no radiologic changes suggesting active tube rculosis, and the sputum cultures for Mycobacterium tuberculosis were Delayed Onset ARDS in Babesiosis (Horowitz, Coletta, Fein)

negative. The patient did not have any of the usual risk factors for severe babesiosis, except for advanced age and travel to two endemic areas. As previously stated, the classic description of severe babesiosis does not include respiratory failure or ARDS as one of its clinical manifestations. This report represents only the second documented report of ARDS following babesiosis. The only other reported case of ARDS attributed to babesiosis occurred approximately 7 weeks after the patient received a blood transfusion contaminated with Babesia.l 0 This patient was admitted with an intraabdominal abscess and during surgery received a blood transfusion. She subsequently presented 6 weeks later with sepsis, and was initially treated for three days with antibiotics. On day 4, the patient was noted to have 10 percent intraerythrocytic parasitemia on a peripheral smear, confirming babesiosis. On day 9, the patient developed acute respiratory failure and ARDS requiring mechanical ventilation. She died on day 15. Postmortem examination revealed findings consistent with diffuse alveolar damage.10 A curious finding in both the currently reported patient and the initial report was the delayed onset of ARDS. In most patients, ARDS will develop within 72 h of the initial insult, and in most cases within 24 h. 11 Our patient developed acute respiratory failure four days into his illness, while the other reported patient developed it after 9 days. This appears to be a unique feature of ARDS after babesiosis. The cause of ARDS after babesiosis is unknown. Information gleaned from the study of sepsis and multiorgan failure in malaria has provided insight into possible pathophysiologic mechanisms in the related but less severe babesiosis. These include endotoxemia (LPS), complement activation, immune complex deposition, cytoadherence, microemboli, and dissiminated intravascular coagulation. 12 Both malaria and babesiosis are associated with elevated levels of endotoxin (LPS), increased vascular permeability, and shock in animal models. 13 It has been suggested that the intraerythrocytic death of these parasites causes sensitization to endotoxin. 13 The source of LPS is uncertain but may be gastrointestinal translocation of the parasite itsel£.14 The latter hypothesis has not yet been proven. In both malaria and babesiosis, higher levels of parasitic density are not necessarily associated with a greater severity of disease. 7 •13 Our patient had 2 percent parasitemia on the peripheral smear which is similar to levels which have resulted in fatal outcomes due to babesiosis. 5 During antibiotic treatment of babesiosis, the parasites may intermittently be absent on peripheral blood smear. Despite a negative blood smear, infection may persist for up to 5 weeks, indicating inadequate eradication of the organism. 6 The delayed onset of ARDS in our patient may have resulted from persistent parasitic infection, 14 despite rapid clearing of his peripheral blood smear. It is also possible that antimicrobial therapy resulted in destruction of organisms with enhanced release of parasitic antigens into the circulation, causing an endotoxin-like challenge and an increase in the inflammatory response. 14 In summary, we report the second case of ARDS after babesiosis. Our patient manifested the classic clinical picture of ARDS, as shown by persistent noncardiogenic pulmonary edema, severe hypoxemia requiring positive end-

expiratory pressure, and low total respiratory system compliance. A unique feature of Babesia-induced ARDS is its delayed onset, greater than 72 h, following initial signs of systemic infection. REFERENCES

1 Ruebush TK, Juranek DD, Chisholm ES, Snow PC, Healy GR, Sulzer AJ. Human babesiosis on Nantucket Island: evidence for self-limited and subclinical infections. N Eng! J Med 1977; 297(15):825-27 2 Grunwaldt E, Barbour AG, Benach JL. Simultaneous occurrence of babesiosis and Lyme disease. N Eng! J Med 1983; 308:1166 3 Gelfand JA. Babesia. In Mandell GL: Principles and practices of infectious diseases, 3rd ed. New York: Churchill Livingstone, 1989; 2119-22 4 Grunwaldt E. Babesiosis on Shelterlsland. NY State J Med 1977; 77:1320-21 5 Meldrum SC, Guthrie SB, White DS, Benach JL, Morse DL. Human babesiosis in New York state: an epidemiological description of 136 cases. Clin Infect Dis 1992; 15:1019-23 6 Francioli PB, Keithly JS, Jones TC, Brandstetter RD, Wolf DJ. Response of babesiosis to pentamadine therapy. Ann Intern Med 1981; 94:326-30 7 Sun T, Tenenbaum MJ, Greenspan J, T eichberg S, Wang RT, Degnan T, et al. Morphologic and clinical observations in human infection with babesiamicroti. JInfect Dis 1983; 148:239-48 8 Salord F, Allaovchiche B. Severe falciparum malaria (21 cases). Intensive Care Med 1991; 17:449-54 9 Chapman WE, Ward PA. The complement profile in babesiosis. J Immunol 1976; 117:935-38 10 Gordon S, Cordon RA, Mazdzer EJ, Valigorsky JM, Blagg NA, Barnes SJ. Adult respiratory distress syndrome in babesiosis. Chest 1984; 86:633-34 11 Sloane PJ, Gee MH, Gottlieb JE, Albertia KH. A multicenter registry of patients with acute respiratory distress syndrome: physiology and outcome. Am Respir 1992; 146:419-26 12 Brooks MH, Keil FW, Sheehy TW, Barry KG. Acute pulmonary edema in falciparum malaria. N Eng! J Med 1968; 279:732-37 13 Clark IA. Does endotoxin cause both the disease and parasite death in acute malaria and babesiosis? Lancet 1978; 2:75-77 14 Cox FEG. Malaria, piroplasmosis, and endotoxin. Nature 1978; 274:312

Astrocytoma Presenting With Apnea and Sinus Arrest* Natarajan Rajagopalan, M.B.B.S.; and Victor Hoffstein , M.D.

Although some vascular lesions of the central nervous system are known to cause abnormalities in the control of breathing, association between astrocytoma and combined· cardiorespiratory abnormalities in the adult is distinctly unusual. We present a case of a 52-year-old man whose only features of astrocytoma consisted of episodes of apnea and sinus arrest followed by prolonged alveolar hypoventilation. These abnormalities resolved after resection of the tumor. We conclude that in patients presenting with respiratory and sinus arrest, *From the Department of Medicine, St. Michael's Hospital, University of Toronto, Ontario, Canada. Reprint requests: Dr. Hoffstein, St. Michael's Hospital , 30 Bond Street, Toronto, ON, Canada MSB1W8 CHEST I 1061 4 I OCTOBER, 1994

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