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Pulmonary Nocardiosis: Report of a Case Complicated by Tuberculosis
Case Report Section Pulmonary Nocardiosis: Report of a Case Complicated by Tuberculosis* EMMETT R. HALL, JR., M.D. and DENTON A. COOLEY, M.D.
Houston, Texas
Although much attention has been given recently to fungus infections of the lung, relatively few cases of pulmonary nocardiosis have been described and in most of them the disease was in the terminal stages. The apparent rarity of the disease is largely due to failure to recognize the clinical manifestations and findings of nocardiosis. Moreover similarity between nocardiosis and pulmonary tuberculosis from a clinical and roentgenographic standpoint and the similar morphology of the causative organisms may lead to an erroneous diagnosis of tuberculosis in many cases of pulmonary nocardiosis. Even greater confusion may arise where both infections coexist. Recently we operated upon a patient with pulmonary nocardiosis and tuberculosis in whom the latter infection was not recognized prior to lobectomy. Specific antituberculosis therapy was instituted 14 days after operation and a dangerous spread of the tuberculosis process was controlled. L. L., a 40 year old Latin-American male was admitted to Methodist Hospital on May 25, 1954 with a diagnosis of pulmonary nocardiosis. Symptoms began about nine months previously and consisted of fever, fatigue, and weight loss of 40 to 45 pounds. For the past 12 years he was employed by a sulphur producing company and was exposed to fine sulphur dust and sulphides. When he consulted his physician in November 1953, three weeks following the onset of cough and hemoptysis, sputum examinations revealed acid-fast organisms with mycelial branching suggestive of Nocardia asteroides. Tubercle bacilli were not isolated. Samples of sputum were used for guinea pig inoculation and the granulomatous lesion formed produced pure cultures of Nocardia asteroidea (Figure 1). . Under his physician's care he received sulfadiazine approximately 6.0 grams daily until the present hospitalization. He became afebrile and the cough was relieved. Sputum examinations were negative for the first several weeks and then again became positive for Nocardia asteroidea, On admission to the hospital he appeared to be well nourished and in good, general condition. There were rales audible over the right upper lobe but no other significant abnormal finding was present. Laboratory studies revealed normal hemogram and urinalysis showed a trace of protein and sugar. Serologic test for syphilis was positive. Sputum examinations revealed acid fast organisms which were presumed to be Nocardia asteroides and results of cultures were not available at the time of thoracotomy. Roentgenograms of the chest revealed dense infiltration and consolidation of the right upper lobe which contained multiple cavities (Figure 2). The remainder of the right lung and the entire left lung were uninvolved. On May 29, 1954, following negative bronchoscopy thoracotomy was performed under ether anesthesia. The pleural space was almost completely obliterated by the inflammatory process. After the adhesions were divided, the lung was carefully palpated. The upper lobe was totally atelectatic and consolidated and the bronchopulmonary nodes were enlarged. Upper lobectomy was done and two nodules were removed from the middle lobe by wedge resection. The lower lobe was completely free of disease. -From the Department of Surgery, Baylor University College of Medieine, and the Surgical Service of the Methodist Hospital. Aided in part by a grant from Cora and Webb Kading Fund for Surgical Research. 453
HALL AND COOLEY
454
April, 1957
After operation he continued on sulfadiazine and blood sulfa level was maintained between 3.6 and 7.2 mgm per cent. In addition he received penicillin and terramycin injections and remained afebrile. Because of a persistent air leak from the thoracotomy tube right phrenic crush was done on the ninth day after operation and the pulmonary leak healed promptly. He remained afebrile and his appetite improved. On the 14th day after thoracotomy bilateral parenchymal infiltration was noted in roentgenograms of the chest (Figure 3) . Sputum was then reported to be strongly positive for M. tuberculosis and cultures of sputum made before operation revealed colonies of the same organism. Fortunately he remained surprisingly well. Streptomycin arid para-aminosalicylic acid was begun and continued during the remainder of the hospital stay. He improved steadily and was discharged from the hospital June 17, 1954. Since discharge he has remained well . Streptomycin and para-aminosalicylic acid were continued for six months. The latest roentgenogram of the the chest revealed resolution of the bilateral pneumonic process and sputum examinations are negative for Nocardia asteroides and Mycobacterium tuberculosis. Pathologic examination of the specimen of the right upper lobe revealed an abscess cavity measuring 3.5 cm. in diameter with the remainder of the lobe atelectatic and infiltrated with a grayish tan necrotic tissue (Figure 4). Microscopic examination of the lung revealed a well-defined granulomatous reaction with tubercles and caseation necrosis. Within occasional Langhans' giant cells and elsewhere were seen elongated bacilliform structures. Acid fast stains of the lymph nodes disclosed irregularly staining acid-fast organisms with inconstant morphology and a tendency to branching.
Discussion The first known case of a human infection by a fungus known as Cladothrix asteroides was reported in 1891 by Eppinger? who described a patient dying of brain abscess from which an aerobic gram-positive, acid-fast actinomyces was identified. In 1888 Nocard-" had reported an acid-fast sporothrix isolated from cows thought to have tuberculosis. The organism in both instances was subsequently proved to be identical and became known as Nocardia asteroides. Isolated cases of pulmonary nocardiosis appeared during the ensuing years and in 1921 Henrici and
FIGURE 1
FIGURE 2
Figure 1: Photograph of culture made of sputum at onset of illness showing typical wrinkled and granular colony of Nocardia asteroides.-Figure 2: Roentgenogram of chest made just prior to operation showing infiltration and cavitation in right upper lobe.
VoL XXXI
PULMONARY NOCARDIOSIS
455
Gardner-" made the first extensive review of the medical literature collecting 26 established cases of nocardiosis, 23 of which were pulmonary, and added another. Since their collected review occasional isolated reports have appeared bringing the total reported cases of pulmonary involvement to 46.2 Nocardia asteroides is an aerobic, gram-positive, acid-fast organism which grows readily on a variety of simple media, the colonies appearing wrinkled and granular (Figure 1). Pigmentation may vary from yellow to an orange red. Culturally and morphologically the organism is closely related to Mycobacterium tuberculosis. Tubercle bacilli vary in length from one to four IL, whereas the organism, N. asteroides, is one IL, or less in length and shows a distinct tendency to branching.v" Nocardia asteroides produces a granulomatous lesion usually containing an exudate in which pink or black granules are demonstrated microscopically. The organism is pathogenic for laboratory animals which frequently die from the toxic effect of inoculated material rather than from extensive invasion of the fungus.t-" In man nocardiosis is usually contacted by air-borne contamination but may be introduced by trauma and small cutaneous puncture wounds. There have been no reported instance of transfer of disease from man to man or animal to man.8 , 16 Symptoms of nocardiosis are usually respiratory including chronic productive cough and occasional hemoptysis. Complaints of malaise, chills, fever, anorexia, weight loss, and night sweats are common . Symptoms of headache, nausea and vomiting may indicate the presence of cerebral involvement a not infrequent complication of the disease according to
FIGURE 3
FIGURE 4
Figure 8 : Roentgenogram of chest made 14 days after operation showing pleural thickening on the right and fresh bronchopneumonic infiltration of the left lung. Figure 4: Photograph of specimen of right upper lobe showing atelectasis, consolidation, and cavitation.
456
HALL AND COOLEY
April. 116'1
some. 1. , 16,19 Metastatic lesions may occur as a result of hematogenous spread," Roentgenologically, an infiltrative process of the lungs is manifested which may lead to multiple cavitations. Drake and Henrici in 1943, showed in animals there was no cross reaction between Nocardia antigen and tuberculin. With early diagnosis and institution of proper therapy the prognosis is favorable. However, in the event of pyemia and metastases the disease is probably fata1. 2 1 Benbow, Smith and Grimson- reported two cases of nocardiosis with pulmonary and subcutaneous involvement that were considered cured. These patients received bed rest, surgical- drainage, vitamins, sulfonamides, iodides, and x-ray. Since then an increasing incidence of cures is noted. 23 Most patients showing favorable results received sulfonamides, however, Hague and associates" in 1949 reported a case of pulmonary nocardiosis in a 64 year old female in which penicillin, streptomycin, and aureomycin, but not sulfonamides, inhibited the organism. In our patient diagnosis of pulmonary nocardiosis was firmly established prior to operation and the systemic manifestations of the disease were adequately controlled by sulfadiazine. Although tuberculosis was suspected from the time of initial examination, identification of the tubercle bacillus was not possible. It may be that subsequent control of the fungus infection by sulfonamide permitted an emergence of the tuberculous process which flourished in an uncontrolled manner. Thus, after operation a dangerous spread of the tuberculous infection occurred while fungus disease remained under control with sulfadiazine. A possible fatal outcome was averted by final recognition of. fulminating pulmonary tuberculosis and institution of appropriate therapy. To our knowledge no previous case of coexisting pulmonary nocardiosis and tuberculosis has been reported. Fortunately the patient made a complete recovery under treatment for both diseases. References will appear in reprints.
Houston, Texas
Although much attention has been given recently to fungus infections of the lung, relatively few cases of pulmonary nocardiosis have been described and in most of them the disease was in the terminal stages. The apparent rarity of the disease is largely due to failure to recognize the clinical manifestations and findings of nocardiosis. Moreover similarity between nocardiosis and pulmonary tuberculosis from a clinical and roentgenographic standpoint and the similar morphology of the causative organisms may lead to an erroneous diagnosis of tuberculosis in many cases of pulmonary nocardiosis. Even greater confusion may arise where both infections coexist. Recently we operated upon a patient with pulmonary nocardiosis and tuberculosis in whom the latter infection was not recognized prior to lobectomy. Specific antituberculosis therapy was instituted 14 days after operation and a dangerous spread of the tuberculosis process was controlled. L. L., a 40 year old Latin-American male was admitted to Methodist Hospital on May 25, 1954 with a diagnosis of pulmonary nocardiosis. Symptoms began about nine months previously and consisted of fever, fatigue, and weight loss of 40 to 45 pounds. For the past 12 years he was employed by a sulphur producing company and was exposed to fine sulphur dust and sulphides. When he consulted his physician in November 1953, three weeks following the onset of cough and hemoptysis, sputum examinations revealed acid-fast organisms with mycelial branching suggestive of Nocardia asteroides. Tubercle bacilli were not isolated. Samples of sputum were used for guinea pig inoculation and the granulomatous lesion formed produced pure cultures of Nocardia asteroidea (Figure 1). . Under his physician's care he received sulfadiazine approximately 6.0 grams daily until the present hospitalization. He became afebrile and the cough was relieved. Sputum examinations were negative for the first several weeks and then again became positive for Nocardia asteroidea, On admission to the hospital he appeared to be well nourished and in good, general condition. There were rales audible over the right upper lobe but no other significant abnormal finding was present. Laboratory studies revealed normal hemogram and urinalysis showed a trace of protein and sugar. Serologic test for syphilis was positive. Sputum examinations revealed acid fast organisms which were presumed to be Nocardia asteroides and results of cultures were not available at the time of thoracotomy. Roentgenograms of the chest revealed dense infiltration and consolidation of the right upper lobe which contained multiple cavities (Figure 2). The remainder of the right lung and the entire left lung were uninvolved. On May 29, 1954, following negative bronchoscopy thoracotomy was performed under ether anesthesia. The pleural space was almost completely obliterated by the inflammatory process. After the adhesions were divided, the lung was carefully palpated. The upper lobe was totally atelectatic and consolidated and the bronchopulmonary nodes were enlarged. Upper lobectomy was done and two nodules were removed from the middle lobe by wedge resection. The lower lobe was completely free of disease. -From the Department of Surgery, Baylor University College of Medieine, and the Surgical Service of the Methodist Hospital. Aided in part by a grant from Cora and Webb Kading Fund for Surgical Research. 453
HALL AND COOLEY
454
April, 1957
After operation he continued on sulfadiazine and blood sulfa level was maintained between 3.6 and 7.2 mgm per cent. In addition he received penicillin and terramycin injections and remained afebrile. Because of a persistent air leak from the thoracotomy tube right phrenic crush was done on the ninth day after operation and the pulmonary leak healed promptly. He remained afebrile and his appetite improved. On the 14th day after thoracotomy bilateral parenchymal infiltration was noted in roentgenograms of the chest (Figure 3) . Sputum was then reported to be strongly positive for M. tuberculosis and cultures of sputum made before operation revealed colonies of the same organism. Fortunately he remained surprisingly well. Streptomycin arid para-aminosalicylic acid was begun and continued during the remainder of the hospital stay. He improved steadily and was discharged from the hospital June 17, 1954. Since discharge he has remained well . Streptomycin and para-aminosalicylic acid were continued for six months. The latest roentgenogram of the the chest revealed resolution of the bilateral pneumonic process and sputum examinations are negative for Nocardia asteroides and Mycobacterium tuberculosis. Pathologic examination of the specimen of the right upper lobe revealed an abscess cavity measuring 3.5 cm. in diameter with the remainder of the lobe atelectatic and infiltrated with a grayish tan necrotic tissue (Figure 4). Microscopic examination of the lung revealed a well-defined granulomatous reaction with tubercles and caseation necrosis. Within occasional Langhans' giant cells and elsewhere were seen elongated bacilliform structures. Acid fast stains of the lymph nodes disclosed irregularly staining acid-fast organisms with inconstant morphology and a tendency to branching.
Discussion The first known case of a human infection by a fungus known as Cladothrix asteroides was reported in 1891 by Eppinger? who described a patient dying of brain abscess from which an aerobic gram-positive, acid-fast actinomyces was identified. In 1888 Nocard-" had reported an acid-fast sporothrix isolated from cows thought to have tuberculosis. The organism in both instances was subsequently proved to be identical and became known as Nocardia asteroides. Isolated cases of pulmonary nocardiosis appeared during the ensuing years and in 1921 Henrici and
FIGURE 1
FIGURE 2
Figure 1: Photograph of culture made of sputum at onset of illness showing typical wrinkled and granular colony of Nocardia asteroides.-Figure 2: Roentgenogram of chest made just prior to operation showing infiltration and cavitation in right upper lobe.
VoL XXXI
PULMONARY NOCARDIOSIS
455
Gardner-" made the first extensive review of the medical literature collecting 26 established cases of nocardiosis, 23 of which were pulmonary, and added another. Since their collected review occasional isolated reports have appeared bringing the total reported cases of pulmonary involvement to 46.2 Nocardia asteroides is an aerobic, gram-positive, acid-fast organism which grows readily on a variety of simple media, the colonies appearing wrinkled and granular (Figure 1). Pigmentation may vary from yellow to an orange red. Culturally and morphologically the organism is closely related to Mycobacterium tuberculosis. Tubercle bacilli vary in length from one to four IL, whereas the organism, N. asteroides, is one IL, or less in length and shows a distinct tendency to branching.v" Nocardia asteroides produces a granulomatous lesion usually containing an exudate in which pink or black granules are demonstrated microscopically. The organism is pathogenic for laboratory animals which frequently die from the toxic effect of inoculated material rather than from extensive invasion of the fungus.t-" In man nocardiosis is usually contacted by air-borne contamination but may be introduced by trauma and small cutaneous puncture wounds. There have been no reported instance of transfer of disease from man to man or animal to man.8 , 16 Symptoms of nocardiosis are usually respiratory including chronic productive cough and occasional hemoptysis. Complaints of malaise, chills, fever, anorexia, weight loss, and night sweats are common . Symptoms of headache, nausea and vomiting may indicate the presence of cerebral involvement a not infrequent complication of the disease according to
FIGURE 3
FIGURE 4
Figure 8 : Roentgenogram of chest made 14 days after operation showing pleural thickening on the right and fresh bronchopneumonic infiltration of the left lung. Figure 4: Photograph of specimen of right upper lobe showing atelectasis, consolidation, and cavitation.
456
HALL AND COOLEY
April. 116'1
some. 1. , 16,19 Metastatic lesions may occur as a result of hematogenous spread," Roentgenologically, an infiltrative process of the lungs is manifested which may lead to multiple cavitations. Drake and Henrici in 1943, showed in animals there was no cross reaction between Nocardia antigen and tuberculin. With early diagnosis and institution of proper therapy the prognosis is favorable. However, in the event of pyemia and metastases the disease is probably fata1. 2 1 Benbow, Smith and Grimson- reported two cases of nocardiosis with pulmonary and subcutaneous involvement that were considered cured. These patients received bed rest, surgical- drainage, vitamins, sulfonamides, iodides, and x-ray. Since then an increasing incidence of cures is noted. 23 Most patients showing favorable results received sulfonamides, however, Hague and associates" in 1949 reported a case of pulmonary nocardiosis in a 64 year old female in which penicillin, streptomycin, and aureomycin, but not sulfonamides, inhibited the organism. In our patient diagnosis of pulmonary nocardiosis was firmly established prior to operation and the systemic manifestations of the disease were adequately controlled by sulfadiazine. Although tuberculosis was suspected from the time of initial examination, identification of the tubercle bacillus was not possible. It may be that subsequent control of the fungus infection by sulfonamide permitted an emergence of the tuberculous process which flourished in an uncontrolled manner. Thus, after operation a dangerous spread of the tuberculous infection occurred while fungus disease remained under control with sulfadiazine. A possible fatal outcome was averted by final recognition of. fulminating pulmonary tuberculosis and institution of appropriate therapy. To our knowledge no previous case of coexisting pulmonary nocardiosis and tuberculosis has been reported. Fortunately the patient made a complete recovery under treatment for both diseases. References will appear in reprints.