Nontuberculous
Mycobacterial Harold
B. Spitz and Jerome
other than M. tubercuM YCOBACTERIA may cause clinical and radiographic losis
manifestatigns in the lung that are similar to those caused by M. tuberculosis. These organisms have been referred to as atypical, anonymous, chromogenic, and unclassified mycobacteria. Wolinsky recently called them notuberculous mycobacteria.6 All mycobacteria are aerobic, nonmotile, acidfast rods. M. tuberculosis grows slowly on enriched laboratory media in the form of white or cream-colored opaque colonies. It grows only at 37%, whereas the nontuberculous mycobacteria grow readily at 2%37”C. M. tuberculosis is pathogenic for guinea pigs, in contradistinction to the nontuberculous mycobacteria. Runyon,’ in his classification of the nontuberculous mycobacteria, used pigmentation as one of the important distinguishing criteria, in addition to morphology and rate of growth. His classification follows: Group I. Photochromogens. These are organisms whose colonies become yellow upon exposure to light. M. kansasii, the most important strain, can cause pulmonary disease, rarely cervical adenitis in children, skeletal disease,and disseminated disease. Middle-aged or elderly white males, particularly with preexisting chronic bronchitis or emphysema, are most frequently infected. Group II. Scotochromogens. Their colonies have a yellow pigment that turns orange on exposure to light. M. scrofulaceum characteristically causescervical adenitis in young children and only rarely produces pulmonary infection or disseminated disease. Group ZZZ.Nonphotochromogens. Their colonies, which require 2-4 wk to attain full growth, are white to beige and rarely show pigment. M. avium and M. intracellulare are so Harold B. Spitz, M.D.: Professor of Radiology;Jerome F. Wiot, M.D.:Professor and Chairman, Department of Radiology. Universiry of Cincinnati College of Medicine. Reprint requests should be addressed to Dr. H. B. Spitz. Department of Radiology, University of Cincinnati College of Medicine. 234 Goodman St., Cincinnati, Ohio 45267. 0 I979 by Grune & Stratton Inc. 0037-I98X/79/I403-0004 $OI.OO/O
244
Pulmonary Disease F. Wiot
similar that common laboratory tests cannot distinguish between them. Wolinsky6 therefore or M. refers to them as M. avium-intracellulare avium complex. They are responsible, just as M. kansasii, for some cases of chronic pulmonary disease in adults and may also cause lymphadenitis in children, skeletal disease, and disseminated disease. Group IV. Rapid growers. Colonies of these organisms are similar in color to those of group III but require only 3-5 days to reach full growth. M. fortuitum and M. cheionei are the organisms of primary interest in this group. They rarely cause pulmonary disease. The primary clinical manifestation of this group is the presence of skin abscesses, but skeletal lesions and disseminated disease have also been reported. Nontuberculous mycobacteria cause chronic pulmonary disease that simulates tuberculosis. The most important pulmonary pathogens are M. kansasii and M. avium-intracellulare. The clinical presentation of nontuberculous mycobacterial pulmonary disease cannot be distinguished from that of typical tuberculosis, There is often a history of previous lung disease, such as pulmonary emphysema or pneumoconiosis. The symptoms are often milder than one would expect for the extent of diseasepresent on the chest film. Particularly in M. avium-intracellulare infection, the symptoms are chronic and slow to develop. In fact, the disease is often discovered on a routine chest film. Fever is often absent or low grade. Hemoptysis is common. A negative or weakly positive skin test, failure to respond to antituberculous drugs, and lack of a history of contact with tuberculosis may suggest the diagnosis. Transmission from person to person rarely if ever occurs. The diagnosis can be made only by identifying the infecting organism bacteriologically. The pathologic changescaused by these organisms are similar to those of M. tuberculosis.
The roentgen findings of nontuberculous mycobacterial pulmonary disease are similar in almost all aspectsto those caused by M. tuberculosis.’ Some differences in the incidence of certain of the roentgen findings do exist. Seminars in Roentgenology, Vol. XIV, No. 3 (July), 1979
NONTUBERCULOUS
MYCOBACTERIAL
PULMONARY
DISEASE
245
Fig 1. M. kansasii infection. There are multiple thin-welled cavities in the right upper lobe and a large single cavity in the left upper lobe. One year later a fungus bell developed in the cavity on the left.
Nontuberculous Mycobacterial Pulmonary Disease Cavitation is more common than in tuberculosis. The cavities are often large, thin-walled, and multiple (Fig. 1). In a series of 187 patients with infection caused by M. kansasii,’ cavities occurred in 96% and were multiple in 88%. They were thin-walled in only a third of the cases.’
The cavities were 4 cm or greater in diameter in 27% (Fig. 2). In another large series,3 the cavities were subpleural in many cases of intracellulare infection, whereas they were more centrally located in the lung in kansasii, scrofulaceum, and cheloni infections. In the 13 cases attributed to Group IV organisms (M. cheloni and M. fortuitum), the cavities were thin-walled and
M. kansasii infection. ExtenFig 2. sive disease on the right with en air-fluid level in the lower cavity. Some nodular infiltrate is present in the left lung. [Reproduced by permission of Radiology Clinics of North America.‘]
SPITZ AND
246
M. kansasiiinfection. (A) Solitary Fig 3. shows that the cavity wall is thick.
cavitary
lesion
in the right upper
almost always less then 4 cm in diameter. In the 18 cases caused by M. kansasii, round, thinwalled cavities similar to those in Group IV were observed, but there were more patients with multiple (three or more) cavities, with an occa-
Fig 4. obliterated.
M. sviurmintr8c8t/uf8re (B) The lateral view
lobe and infiltrate
WIOT
in the left base. (6) Tomogram
sional cavity of 4 cm or more in diameter. In a series of M. kansasii infections, several patterns were described:’ (1) One predominant cavity with little (8%), moderate (28%), or extensive ( 11%) surrounding parenchymal disease (Fig.
infection. (Al Scattered lesions in the right lung. The upper confirms middle lobe infiltrate without cavitation.
part of the right
heart
border
is
NONTUBERCULOUS
MYCOBACTERIAL
PULMONARY
DISEASE
3). (2) Multiple cavities with minimal to moderate (25%) or extensive (13%) surrounding disease. (3) Small or large parenchymal infiltrate with little or no cavitation (Fig. 4). There is even a stronger predilection for upper lobe involvement than in typical tuberculosis (Figs. l-3). In the series of M. kansasii infection,’ the upper lobes were affected in all but 1 of 80 patients in whom the disease was confined to a single lobe. This exception involved the superior segment of the right lower lobe. No patient had disease limited to the anterior segment of an upper lobe. In another large series,3 90% of the cases involved the upper lobes. The right upper lobe is infected almost three times as often as the left. The exudative type of lesion is rare, as is hematogenous spread. Diffuse nodular lesions, bronchiectasis, and empyema have been observed with M. avium-intracellulare infection. Pleural effusion, a hallmark of infection with hf. tuberculosis, is uncommon, as is hilar adenopathy. Preexisting pulmonary disease is common, including chronic bronchitis, bronchiectasis, emphysema, typical tuberculosis, pneumoconio-
247
sis (Fig. 5), and chronic aspiration. In the kansasii series,’ 61% of the patients had chronic obstructive pulmonary disease and 39% had bullous emphysema. Progression of the disease (Fig. 6) is manifested by4 spread of noncavitary foci of pneumonic infiltration into the adjacent pulmonary tissue, enlargement of cavities, pleural effusion, infection of preexisting bullae, and superimposed infection by gram-negative bacilli, fungi, and M. tuberculosis.
Distant dissemination is rare and is almost always associated with underlying debilitating disease,immunosuppressive therapy, or lymphoma. M. kansasii is sensitive to drugs. M. aviumintracellufare strains usually are drug resistant. Surgical treatment is often necessaryfor control of drug-resistant cases. Although the clinical and radiographic findings in mycobacterial pulmonary disease are similar to those of typical tuberculosis, certain characteristics of the disease may suggest its presence. These include multiple, large, thinwalled cavities (with relatively little surrounding reaction) involving one or both upper lobes;
SPITZ AND
248
Fig 6. M. kansasii infection. (A) Bilateral upper lobe cavitary disease is superimposed on bullous ball is present in the right upper lobe cavity. (B) Eleven months later there is spread of pneumonic Air-fluid levels have appeared in bullae at both lung bases.
preexisting chronic lung disease; absence of pleural disease;and relative drug resistance. The cultural characteristics readily separate these groups of organisms from each other and from M. tuberculosis. Recognition of nontuberculous mycobacterial pulmonary diseaseand separation
WIOT
emphysema. A fungus infiltrate on the left.
of it from M. tuberculosis infection are important because some strains of nontuberculous mycobacteria are drug resistant and require a more vigorous chemotherapeutic regimen or even surgery.
REFERENCES 1. Christensen EE, Dietz GW, Ahn, CH, et al: Radiographic manifestations of pulmonary Mycobacterium kansasii infections. Am J Roentgenol 131:985-993, 1978 2. Runyon EH: Anonymous mycobacteria in pulmonary disease. Med Clin North Am 43:273-290, 1959 3. Shimoide H, et al: Roentgenological studies of lung disease due to mycobacteria other than tubercle bacilli; The first report: On the difference in the radiographic feature among the various species of atypical mycobacteria. Kekkaku 52 (8):391-398.1977
4. Shimoide H, et al: Roentgenological studies of lung disease due to mycobacteria other than tubercle bacilli: On the course of the progression of pulmonary lesions in the fatal cases. Kekkaku 53 (2):99-105, 1978 5. Wiot JF, Spitz HB: Atypical pulmonary tuberculosis. Radio1 Clin North Am 1 I (1):191-196, 1973 6. Wolinsky E: Nontuberculous mycobacteria and associated diseases. Am Rev Resp Dis 119:107-159, 1979
Mycobacterial Harold
B. Spitz and Jerome
other than M. tubercuM YCOBACTERIA may cause clinical and radiographic losis
manifestatigns in the lung that are similar to those caused by M. tuberculosis. These organisms have been referred to as atypical, anonymous, chromogenic, and unclassified mycobacteria. Wolinsky recently called them notuberculous mycobacteria.6 All mycobacteria are aerobic, nonmotile, acidfast rods. M. tuberculosis grows slowly on enriched laboratory media in the form of white or cream-colored opaque colonies. It grows only at 37%, whereas the nontuberculous mycobacteria grow readily at 2%37”C. M. tuberculosis is pathogenic for guinea pigs, in contradistinction to the nontuberculous mycobacteria. Runyon,’ in his classification of the nontuberculous mycobacteria, used pigmentation as one of the important distinguishing criteria, in addition to morphology and rate of growth. His classification follows: Group I. Photochromogens. These are organisms whose colonies become yellow upon exposure to light. M. kansasii, the most important strain, can cause pulmonary disease, rarely cervical adenitis in children, skeletal disease,and disseminated disease. Middle-aged or elderly white males, particularly with preexisting chronic bronchitis or emphysema, are most frequently infected. Group II. Scotochromogens. Their colonies have a yellow pigment that turns orange on exposure to light. M. scrofulaceum characteristically causescervical adenitis in young children and only rarely produces pulmonary infection or disseminated disease. Group ZZZ.Nonphotochromogens. Their colonies, which require 2-4 wk to attain full growth, are white to beige and rarely show pigment. M. avium and M. intracellulare are so Harold B. Spitz, M.D.: Professor of Radiology;Jerome F. Wiot, M.D.:Professor and Chairman, Department of Radiology. Universiry of Cincinnati College of Medicine. Reprint requests should be addressed to Dr. H. B. Spitz. Department of Radiology, University of Cincinnati College of Medicine. 234 Goodman St., Cincinnati, Ohio 45267. 0 I979 by Grune & Stratton Inc. 0037-I98X/79/I403-0004 $OI.OO/O
244
Pulmonary Disease F. Wiot
similar that common laboratory tests cannot distinguish between them. Wolinsky6 therefore or M. refers to them as M. avium-intracellulare avium complex. They are responsible, just as M. kansasii, for some cases of chronic pulmonary disease in adults and may also cause lymphadenitis in children, skeletal disease, and disseminated disease. Group IV. Rapid growers. Colonies of these organisms are similar in color to those of group III but require only 3-5 days to reach full growth. M. fortuitum and M. cheionei are the organisms of primary interest in this group. They rarely cause pulmonary disease. The primary clinical manifestation of this group is the presence of skin abscesses, but skeletal lesions and disseminated disease have also been reported. Nontuberculous mycobacteria cause chronic pulmonary disease that simulates tuberculosis. The most important pulmonary pathogens are M. kansasii and M. avium-intracellulare. The clinical presentation of nontuberculous mycobacterial pulmonary disease cannot be distinguished from that of typical tuberculosis, There is often a history of previous lung disease, such as pulmonary emphysema or pneumoconiosis. The symptoms are often milder than one would expect for the extent of diseasepresent on the chest film. Particularly in M. avium-intracellulare infection, the symptoms are chronic and slow to develop. In fact, the disease is often discovered on a routine chest film. Fever is often absent or low grade. Hemoptysis is common. A negative or weakly positive skin test, failure to respond to antituberculous drugs, and lack of a history of contact with tuberculosis may suggest the diagnosis. Transmission from person to person rarely if ever occurs. The diagnosis can be made only by identifying the infecting organism bacteriologically. The pathologic changescaused by these organisms are similar to those of M. tuberculosis.
The roentgen findings of nontuberculous mycobacterial pulmonary disease are similar in almost all aspectsto those caused by M. tuberculosis.’ Some differences in the incidence of certain of the roentgen findings do exist. Seminars in Roentgenology, Vol. XIV, No. 3 (July), 1979
NONTUBERCULOUS
MYCOBACTERIAL
PULMONARY
DISEASE
245
Fig 1. M. kansasii infection. There are multiple thin-welled cavities in the right upper lobe and a large single cavity in the left upper lobe. One year later a fungus bell developed in the cavity on the left.
Nontuberculous Mycobacterial Pulmonary Disease Cavitation is more common than in tuberculosis. The cavities are often large, thin-walled, and multiple (Fig. 1). In a series of 187 patients with infection caused by M. kansasii,’ cavities occurred in 96% and were multiple in 88%. They were thin-walled in only a third of the cases.’
The cavities were 4 cm or greater in diameter in 27% (Fig. 2). In another large series,3 the cavities were subpleural in many cases of intracellulare infection, whereas they were more centrally located in the lung in kansasii, scrofulaceum, and cheloni infections. In the 13 cases attributed to Group IV organisms (M. cheloni and M. fortuitum), the cavities were thin-walled and
M. kansasii infection. ExtenFig 2. sive disease on the right with en air-fluid level in the lower cavity. Some nodular infiltrate is present in the left lung. [Reproduced by permission of Radiology Clinics of North America.‘]
SPITZ AND
246
M. kansasiiinfection. (A) Solitary Fig 3. shows that the cavity wall is thick.
cavitary
lesion
in the right upper
almost always less then 4 cm in diameter. In the 18 cases caused by M. kansasii, round, thinwalled cavities similar to those in Group IV were observed, but there were more patients with multiple (three or more) cavities, with an occa-
Fig 4. obliterated.
M. sviurmintr8c8t/uf8re (B) The lateral view
lobe and infiltrate
WIOT
in the left base. (6) Tomogram
sional cavity of 4 cm or more in diameter. In a series of M. kansasii infections, several patterns were described:’ (1) One predominant cavity with little (8%), moderate (28%), or extensive ( 11%) surrounding parenchymal disease (Fig.
infection. (Al Scattered lesions in the right lung. The upper confirms middle lobe infiltrate without cavitation.
part of the right
heart
border
is
NONTUBERCULOUS
MYCOBACTERIAL
PULMONARY
DISEASE
3). (2) Multiple cavities with minimal to moderate (25%) or extensive (13%) surrounding disease. (3) Small or large parenchymal infiltrate with little or no cavitation (Fig. 4). There is even a stronger predilection for upper lobe involvement than in typical tuberculosis (Figs. l-3). In the series of M. kansasii infection,’ the upper lobes were affected in all but 1 of 80 patients in whom the disease was confined to a single lobe. This exception involved the superior segment of the right lower lobe. No patient had disease limited to the anterior segment of an upper lobe. In another large series,3 90% of the cases involved the upper lobes. The right upper lobe is infected almost three times as often as the left. The exudative type of lesion is rare, as is hematogenous spread. Diffuse nodular lesions, bronchiectasis, and empyema have been observed with M. avium-intracellulare infection. Pleural effusion, a hallmark of infection with hf. tuberculosis, is uncommon, as is hilar adenopathy. Preexisting pulmonary disease is common, including chronic bronchitis, bronchiectasis, emphysema, typical tuberculosis, pneumoconio-
247
sis (Fig. 5), and chronic aspiration. In the kansasii series,’ 61% of the patients had chronic obstructive pulmonary disease and 39% had bullous emphysema. Progression of the disease (Fig. 6) is manifested by4 spread of noncavitary foci of pneumonic infiltration into the adjacent pulmonary tissue, enlargement of cavities, pleural effusion, infection of preexisting bullae, and superimposed infection by gram-negative bacilli, fungi, and M. tuberculosis.
Distant dissemination is rare and is almost always associated with underlying debilitating disease,immunosuppressive therapy, or lymphoma. M. kansasii is sensitive to drugs. M. aviumintracellufare strains usually are drug resistant. Surgical treatment is often necessaryfor control of drug-resistant cases. Although the clinical and radiographic findings in mycobacterial pulmonary disease are similar to those of typical tuberculosis, certain characteristics of the disease may suggest its presence. These include multiple, large, thinwalled cavities (with relatively little surrounding reaction) involving one or both upper lobes;
SPITZ AND
248
Fig 6. M. kansasii infection. (A) Bilateral upper lobe cavitary disease is superimposed on bullous ball is present in the right upper lobe cavity. (B) Eleven months later there is spread of pneumonic Air-fluid levels have appeared in bullae at both lung bases.
preexisting chronic lung disease; absence of pleural disease;and relative drug resistance. The cultural characteristics readily separate these groups of organisms from each other and from M. tuberculosis. Recognition of nontuberculous mycobacterial pulmonary diseaseand separation
WIOT
emphysema. A fungus infiltrate on the left.
of it from M. tuberculosis infection are important because some strains of nontuberculous mycobacteria are drug resistant and require a more vigorous chemotherapeutic regimen or even surgery.
REFERENCES 1. Christensen EE, Dietz GW, Ahn, CH, et al: Radiographic manifestations of pulmonary Mycobacterium kansasii infections. Am J Roentgenol 131:985-993, 1978 2. Runyon EH: Anonymous mycobacteria in pulmonary disease. Med Clin North Am 43:273-290, 1959 3. Shimoide H, et al: Roentgenological studies of lung disease due to mycobacteria other than tubercle bacilli; The first report: On the difference in the radiographic feature among the various species of atypical mycobacteria. Kekkaku 52 (8):391-398.1977
4. Shimoide H, et al: Roentgenological studies of lung disease due to mycobacteria other than tubercle bacilli: On the course of the progression of pulmonary lesions in the fatal cases. Kekkaku 53 (2):99-105, 1978 5. Wiot JF, Spitz HB: Atypical pulmonary tuberculosis. Radio1 Clin North Am 1 I (1):191-196, 1973 6. Wolinsky E: Nontuberculous mycobacteria and associated diseases. Am Rev Resp Dis 119:107-159, 1979
