Treatment of Unusual Pulmonary Amebic Abscess with Chloroquine

Treatment of Unusual Pulmonary Amebic Abscess with Chloroquine * ALAN E. LINDSAY, M.D., WAYNE H. GOSSARD, M.D., and JOHN S. CHAPMAN, M.D. Dallas, Texas Pleuro-pulmonary amebiasis complicates amebic hepatic abscesses in about 15 per cent of the reported cases, as indicated by Ochsner and DeBakeyl in their comprehensive review of the subject in 1936. The usual pulmonary complication consists either of a lower lobe abscess or a broncho-hepatic fistula, both of which arise by direct extension of an hepatic abscess through the diaphragm. Craig2 states that "the lower right lobe of the lung is the site of the pulmonary amebic abscess almost invariably." Amebic empyema arises in 17 to 33 per cent of the reported cases. Primary amebic broncho-pulmonary involvement has been reported, but in these cases it cannot be said with certainty that amebic colitis was not present. Ochsner and DeBakeyl found that "hematogenous" pulmonary abscesses with independent liver abscesses occurred in 10.4 per cent of 153 cases collected from the literature and in none of their own 13 cases. Craig2 refers to Girgis' two fatal cases of multiple pulmonary and hepatic amebic abscesses in which Endamoeba histolytica could be demonstrated in emboli in the pulmonary arterial vessels, thus supporting the view that hematogenous dissemination of the parasite may occur, presumably from the liver through the right side of the heart to the lung. In the absence of demonstrable contiguity between hepatic and pulmonary lesions, one must assume that this type of blood-borne dissemination may occur. The following case report is of interest both because of the unusual location of the pulmonary lesion and. the fact that Emetine alone failed to effect a clinical cure, while subsequent Chloroquine therapy caused a complete clearing of the pathological process. The patient, M. E., a 54 year old white male painter, was admitted to the Dallas City-County Tuberculosis Sanitorium on october 13, 1949 for study of a prolonged pulmonary infection. He had been in good health until about four months prior to admission when, following a vacation at the seacoast, he began to note a cough productive of brownish material. His cough became steadily worse, and on one occasion he noted a ·From the Department of Internal Medicine, Southwestern Medical College of the University of Texas and the Dallas City-County Hospital System, Woodlawn Hospital, Dallas, Texas. 533

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transient pleuritic pain at the right costal margin. His other symptoms included anorexia, weakness, and malaise, but no chills or fever. Penicillin and sulfadiazine were administered without effect. A chest x-ray film taken after this therapy was interpreted as "possible virus pneumonia," and over the next 30 days he was given three courses of aureomycin with no remission of his symptoms. About three weeks before admission, following an episode of frank hemoptysis, he consulted a phthisiologist who recommended hospitalization at this institution, an infiltrative and cavitary lesion having been noted on the chest roentgenogram. A sputum examination was negative for acid-fast bacilli at that time. During the ensuing three weeks while he awaited admission, there were occasional temperature rises to 100 degrees F. and all his systemic symptoms continued. At the time of admission he had lost 15 pounds. Past history revealed excellent previous health with no known exposure to tuberculosis. He had received adequate anti-luetic therapy 11 years before admission. Also 11 years prior to his admission a three year old daughter had died from dysentery of unknown type. Physical examination revealed a temperature of 99 degrees F., pulse of 80, blood pressure of 140/90. He was well developed but showed signs of weight loss. The trachea was deviated slightly to the right. Examination of the chest failed to reveal any definite sign of intrapulmonary disease. The liver was palpable four centimeters below the right costal margin and was not tender. The remainder of the physical examination was not remarkable. His initial laboratory studies showed a normal urinalysis, hemoglobin of 15.0 Gm.l100 cc., hematocrit of 48. The white blood cell count was 13,800 with three band forms, 66 segmented forms, two eosinophiles, and 29 lymphocytes. The sputum was green and purulent and was negative for acid-fast bacilli on two smears and two concentrations. Blood urea, blood sugar, and serum proteins were normal. The sedimentation rate was 25 mm./hour. Cephalin-Cholesterol flocculation test was 2 plus in 48 hours, and 8 per cent of Bromsulfaphthalein was retained at 45 min-

FIGURE 1

FIGURE 2

Figure 1: Appearance of the chest roentgenogram prior to therapy with

Emetine.-Figure 2: Appearance of the chest roentgenogram at the completion of Emetine therapy.

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utes. Chest roentgenogram_ revealed an infiltrative and cavernous lesion involving the right upperto~lttgUre 1). TUbercuUn 1:1000 was negative and a routine sputum culture showed only normal flora. During his first three weeks in the hospital he was afebrile and asymptomatic except for a cough productive of about one ounce of green purulent sputum daily. Bronchoscopy failed to reveal any evidence of bronchogenic carcinoma and the bronchial secretions aspirated at the time of bronchoscopy were negative both for tumor cells and acid-fast bacilli. On November 7,1949, his temperature spiked to 102.4 degrees F., malaise and anorexia became marked, and concomitantly the liver became larger and quite tender. The white blood cell count rose to 22,000 with a slight left shift, and the sputum became rusty brown in· color. The following day motlle trophozoites of Endamoeba histolytica were found in the sputum. stool examInation were negative for amebae. A course of Emetine, one grain daily for 10 days, was instituted with diminution in fever, but at the end of this time there was no appreciable change in his clinical symptoms (Figure 3>' His sputum remained positive for trophozoites and the chest roentgenogram was unchanged (Figure 2). Because he had shown little improvement after Emetine, Aralen (Chloroquine) was started in doses of 1.0 Gram daily for two days followed by 0.5 Gram dally for 18 days. Procaine penic1ll1n, 600,000 units daily, was also given to control possible secondary infection. By the end of one week after the institution of Chloroquine therapy, his cough was m1n1mal and the sputum no longer rusty. It was after 10 days of Chloroquine therapy that the amebae disappeared from the sputum, and only at this time was there demonstrable roentgenographic improvement (Figure 4). He was then given a 10 day course of Carbarsone, and was discharged on December 19, 1949, to be followed as an out-patient. Chest Nov. 7

10

13

16

19

22

25

28

30

0

103

Penicillin 600,000 C.(.

B)N?it'iDd

dail~

Y+-

Dec. II Chlol"oquine 0.5e-rn. dail~

FIGURE 3: Chart demonstrating the patient's febrile course during period of therapy.

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x-ray f11m at the time of discharge revealed marked clearing of the right apex with only questionable cavitation. The white blood cell count was normal and his cough had completely disappeared. Subsequent roentgenograms as an out-patient have shown progressive clearing of the lesion until at present, six months after discharge, no signs of pulmonary disease are present (Figure 5). He is working actively and his weight has increased to its normal level.

Comments The location of this patient's amebic abscess in the right upper lobe of the lung, a~d the striking resemblance to moderately advanced pulmonary tuberculosis delayed the correct diagnosis until almost three weeks after he first came under study, and it was only when fever, leukocytosis, the tender enlarged liver, and the rusty-brownish sputum appeared that the diagnosis was suspected and confirmed. Of interest also is the fact that Emetine, which for years has been the only therapeutic agent of real value in cases of extraintestinal amebiasis, failed to eradicate the parasites from the lung or to cause significant roentgenographic improvement in spite of a satisfactory febrile response. Consequently, it was decided to employ Aralen (Chloroquine) to effect full therapeusis. Chloroquine, 7-chloro-4- (4-diethylamino-l-methylbutyl-amino) quinoline, one of the 4-aminoquinoline derivatives studied during recent years because of its anti-malarial activity, has shown increasing usefulness in the treatment of hepatic amebiasis.M,lI It has been shown in studies in rats6 that the tissue/plasma con-

FIGURE 4

FIGURE 5

Figure 4: Appearance of the chest roentgenogram at the completion of

therapy with Chloroqulne.-Ffgure 5: Appearance of the chest roentgenogram seven months after completion of therapy.

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centration of Chloroquine is 420 for liver and 640 for lung tissue. On the basis of these studies,·· then, 'it was felt· that Chloroquine might be a useful agent in this case. Only after 7 to 10 days of Chloroquine therapy did roentgenographic improvement, disappearance of cough and accordingly disappearance of amebic trophozoites from the sputum, and improvement in systemic symptoms (increase in weight and appetite) occur. An interesting parallel may be drawn to Conan's eight cases of amebic liver abscess in three of which clinical response was noted only after Chloroquine therapy was instituted.3 We used the dosage of Chloroquine suggested by Conan. The only toxic manifestations noted were transient nausea, vomiting, and numbness and tingling in the fingers. It was noted that the nausea and vomiting largely disappeared when the dose was diminished from 1.0 Gram to 0.5 Gram dally. SUMMARY A case of pulmonary amebic abscess of the right upper lobe with amebic hepatitis is reported in which hematogenous spread of the amebic parasites from liver to lung was the most probable pathogenetic likelihood. Since E~etine alone failed to cause a satisfactory response, and Chloroquine induced complete clinical remission, it is felt that Chloroquine is a useful agent in cases of pleuropulmonary amebiasis.

RESUMEN

Un caso de absceso pulmonar ambiano en el 16bulo superior derecho con hepatitis amibiana se refiere, en el que la diseminaci6n hemat6gena de los parasitos ambianos del hlgado fue la posib1l1dad patogenica mas verosimil. Cuando la emetina por si sola no di6 resultado satisfactorio, la cloroquina obtuvo una remlsi6n completa y por eso se cree que la cloroquina sea un agente tltil en la amibiasis pleuro-pulmonar. RESUME

Les auteurs rapportent une observation d'abc~ amibien du poumon, localise au lobe superieur droit, etassocie a une hepatite amibienne. Ds pensent que la voie sanguine a ete la plus vraisemblable pour expliquer Ie passage des amibes du foie au poumon. Etant donne que l'emetine a elle seule ne put amener une amelioration et que la chloroquine a permis une guerlson clinique complete, les auteurs estiment que la chloroquine est un moyen therapeutique utile dans les cas d'amibiase pleuro-pulmonaire. REFERENCES 1 OChsner, A. and DeBakey, M.: "Pleuropulmonary Complications of Ameb1as1s," J. Thoracjc Surg., 5:225,1936.

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2 Craig, C. F.: "The Etiology, Diagnosis, and Treatment of Amebiasis," The Williams and Wilkins Co., Baltimore, 1944. 3 Conan, N. J. Jr.: "The Treatment of Hepatic Amebiasis with Chloroquine," Am. J. Med., 6:309, 1949. 4 Murgatroyd, F. and Kent, R. P.: "Refractory Amebic Liver Abscess Treated by Chloroquine," T. Roy. Soc. Trap. Med. and HVg., 42:15, 1948. 5 Emmett, J.: "Refractory Amebic Abscess of the Liver Treated with Chloroquine," J.A.M.A., 141 :22, 1949. 6 Berliner, R. W., Earle, D. P. Jr., Taggart, J. V., Zubrod, C. G., Welch, W. J., Conan, N. J., Bauman, E., Scudder, S. T. and Shannon, J. A.: "Studies on the Chemotherapy of the Human Malarias. VI. The Physiological Disposition, Antimalarial Activity, and Toxicity of Several Deriyatives of 4-Aminoquinoline," J. Clin. Invest., 27:98, 1948. .