Pulmonary lesions due to opportunist mycobacteria

Clin. Radiol. (1975) 26, 461-469

PULMONARY LESIONS DUE TO OPPORTUNIST MYCOBACTERIA (REVIEW INCLUDES 30 CASES OF M. KANSASII INFECTIONS) D. H. ANDERSON*, P. GRECH*~, R. H. T O W N S H E N D * and A. E. JEPHCOTT~

From Lodge Moor Hospital, Redmires Road, Sheffield* and Public Health Laboratory, Sheffield? The apparent increase in the incidence of opportunist mycobacterial pulmonary infection is assessed. The clinical, bacteriological and radiological characteristics of 34 cases of such infections seen over a period of ten years in Sheffield are reviewed. The typical radiological appearances consisting of cavities, fibrosis and opacities are described and illustrated. There has been in the past conflicting reports on the specificity of such radiological features; it is concluded that although such appearances are not pathognomonic, their presence should arouse suspicion of such an infection and this should be confirmed or refuted by bacteriological investigations.

FROM time to time mycobacteria other than M. tuberculosis cause respiratory disease in man. These organisms are grouped together as the so-called opportunist mycobacteria and their significance seems to be increasing as classical tuberculosis declines. This is partly due to a relative increase in their numbers due to the reduction in true M. tuberculosis infections and also to a real increase (Marks, 1969), possibly as they fill the ecological niche left unoccupied by the eradication of tuberculosis from the community. OBJECTIVE Out of the 702 adult patients attending the Sheffield Chest Clinics for pulmonary mycobacterial infections over a period of ten years (1964-73 inclusive) and from whose sputa acidfast bacilli were isolated, 34 were found to be infected not by M. tuberculosis but by one of the closely related opportunist mycobacteria - giving an incidence of just under 5 %. The purpose of this paper is to review the social, clinical, bacteriological and radiological features of these 34 cases in the hope that such a review with illustrations might increase awareness of such infections and help in earlier identification.

but only those cases where clinical and radiological details are available, and where the organisms have been accurately identified and established as clinically significant are included in this survey. Infections were judged to be significant if in the complete absence of positive cultures for M. tuberculosis, during the current illness, a patient yielded repeated isolations of one of the opportunist mycobacteria. These strict criteria have led to the exclusion of many patients. Thirty-four (29 males and 5 females) are included in this analysis, ranging in age from 33 years to 70 years. The average age at the first attendance was 51.6 years. Age and sex incidence are shown in the histogram (Fig. I). Twenty of the 29 male patients (or 69 ~ ) gave an occupational history of exposure to dust or chemicals (Table 1) but none of the females reported any relevant occupational exposure. BACTERIOLOGY

The opportunist mycobacteria are diverse in nature and a degree of classification is essential. The first classification was made by Runyon (1959). He separated them into four groups based on pigment production and rate of growth. Group I (Photochromogens) produced a yellow pigment only when exposed to light. Group II (Scotochromogens) developed their colour in light MATERIAL or darkness. Group lII did not produce a pigment Opportunist mycobacteria were isolated from and Group IV contained all the rapidly growing at least 81 patients during the period under review, strains. This classification correlated fairly well $ Requests for reprints to P. Grech, Radiology Depart- with virulence. Unfortunately saprophytes and parasites coexisted within his groupings and the ment, Lodge Moor Hospital, Sheffield_ 461 30

462

CLINICAL

RADIOLOGY

race

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FIG. 1 Histogram showing the sex and age incidence of the 34 cases of opportunist mycobacterial infections reviewed.

variable properties of some species prevented their classification. In the main only Groups I and III contained species capable of damaging the lung; and whereas those of Group I tended to produce less severe disease, those of Group III produced a disease closely akin to classical pulmonary tuberculosis. Other classifications have since been made with greater differentiation of species and with claims of better correlation of groupings with virulence (Collins, 1962; Marks and Richards, 1962; Marks, 1972), and currently speciation of most isolates has become possible. Thirty of our isolates were of M. kansasii, two of M. intracellulare, one of M. scrofulaceurn and one of M. fortuitum. M O D E OF PRESENTATION

The mode of presentation was variable. In a number of cases symptoms were absent or minimal and the disease was discovered on routine Mass Miniature Radiography. In others symptoms such as cough, lassitude or dyspnoea were present and caused the referral; while in a few cases the

investigation of other conditions led to the discovery of the pulmonary lesion. In most cases, however, an exacerbation of symptoms of chronic chest disease led to the identification of the infection. In general the presenting symptoms were not materially different from those found in sufferers from pulmonary tuberculosis. RADIOLOGY Postero-anterior and lateral radiographs of 34 patients, including those taken at first attendance and follow-up together with tomographs of the relevant lesion, were reviewed. The findings are summarised in Table 2, giving the location and the description of the lesion, noting the presence of any infiltration or spread, pleura1 reaction or calcification. Radiological evidence of any other associated pulmonary disease was recorded and finally the radiological progress of each individual was reviewed. In the past there has been controversy about the specificity of the radiological appearances of the pulmonary lesions. We agree with the views of

PULMONARY LESIONS DUE TO OPPORTUNIST MYCOBACTERIA

463

TABLE ] DETAILSOF 34 CASESOr OPPORTUNISTMYCOBACTERIALINFECTION Cas No

Name

Sex

1 2 3

M.A. J.B. O.B.

F M M

4 5 6 7

A.B. H.B.R. A.C. M.C.

8

C.C.

9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34

L.C. J.G. A.G. H.L. H.M. R.M. H.N. G.P. F.R.

M M M F M M M M M M M M F M

H.R_

M

D.R. R.S. G.S. A.S. J.T. J.E.T. J.V. L.W. A.W. F.B. H.H. J.M. D.B. A.C. K.N. R.W.

M M M F M M M M M M M M M M F M

Age first attendance 47 53

38 55 59 47 48 45 58 56 70 67 48 64 49 39 37 66 34 66 46 70 64 55 50 62 61 48 51 44 30 49 33 48

Myeobaeterium kansasff kansasff kansasii kansasii kansasii kansasii kansasii kansasff kansasff kansasii kansasff kansasii kansasii kansasii kansasii kansasff kansasii kansasff kansasii kansasii kansasii kansasii kansasii kansasii kansasii kansasii kansasii kansasii kalrsasii kansasii intracellulare bttracellalare scrofulaceum fortuitum

most workers (Chapman, 1962; Heitzman, Bornhurst a n d Russell, 1968; Cook, Riddell a n d Simon, 1971) that although the radiological appearances are n o t p a t h o g n o m o n i c , there are certain special features which should make one aware of the possibility of such a n infection. TREATMENT

AND

PROGNOSIS

I n all cases sensitivity tests were carried out on the o p p o r t u n i s t mycobacteria isolated a n d in all resistance to PAS a n d I N A H was found. Partial resistance to streptomycin was also f o u n d in most cultures of M . kansasii b u t all proved to be sensitive to most of the newer drugs a n d in particular to ethionomide, e t h a m b u t o l a n d rifampicin. I n

Occupation - i f relevant

Toolmaker (later foreman) Slinger Grinder Steel plate polisher Steel worker Fettler Grinder Steel worker Sheet metal worker Steel moulder Exposure to chemical fumes Grinder Steel press operator

Grinder Coal miner Oxyacetylene cutter Steel worker Industrial painter Metal turner Miner

the early cases treatment was started with the then s t a n d a r d anti-tuberculous drugs - streptomycin, PAS a n d I N A H and was switched to others as the results of the sensitivity tests became available. I n recent years e t h a m b u t o l or rifampicin were often used from the beginning and ethionamide added later to replace I N A H . I n one case (No. 13) resection was carried out to deal with spreading disease n o t controlled by the drugs then available. A p a r t from this case chemotherapy proved effective in all cases - s p u t u m conversion being achieved a n d healing with fibrosis a n d cavity shrinkage taking place. Of the 34 patients u n d e r review ten have died from causes unrelated to their opportunist infection after a n average follow-up period of 6,6 years.

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FIG. 3 (Case 31). A lesion very similar to that seen in Fig. 2. The Mass Radiography X-ray (A) showed a small cavity in the left upper lobe. Tomograph (B). M . intracellulare were repeatedly cultured from the patient's sputum. The lesion healed within four months of treatment.

FIG. 4 Mass Radiography chest X-ray (A) of a 47-year-old woman (Case 1) which showed multiple cavities in the right apex. Tomograph (B). She was symptom-free but acid-fast bacilli were repeatedly found on sputum smears. Culture revealed M. kansasii. These cavities shrank and healed within ten months.

P U L M O N A R Y LESIONS DUE TO O P P O R T U N I S T MYCOBACTERIA

DISCUSSION Reports of patients with clinical disease caused by the opportunist mycobacteria have been increasing over the last decade (Keller and Runyon, 1964; Heitzman, Bornhurst and Russell, 1968; Seibert and Trabisky, 1969; Cook, Riddell and Simon, 1971). Improvements in bacteriological techniques and awareness have led to the separation of these infections from those of M. tuberculosis. This is of considerable importance in the management and treatment. Most of our isolates (30 out of 34 cases) were of M. kansasii - a photochromogenic member of Runyon's Group I. Two were of the Aviumintracellulare complex, which falls in Runyon's Group III. A case of M. scrofulaceum falls into Runyon's Group II; these organisms are usually not regarded as pathogenic and since these were

467

isolated on more than one occasion in only a single patient in our series, their significance is accordingly dubious. Many single isolates o f other atypical mycobacteria ( e . g . M . xenopii) were made but have not been included due to lack of evidence of pathogenicity. One patient yielded repeated cultures of M. fortuitum. The presence of this organism is considered to result from a failure of clearance rather than from active bacterial invasion, and any tissue damage produced to be of an immunological nature (Marks and Jenkins, 1971). We agree with Cook and his colleagues (1971) that these infections show the same social distribution as those of tuberculosis. As in most other similar surveys, a strong association with preexisting pulmonary diseases h a s been noted, especially emphysema and pneumoconiosis. Twenty-one of the 29 male patients in this series

FIG. 5 (Case 15). Routine mass radiograph (A) of a 49-year-old moulder showed a large, thin-walled, oval cavity with several roundish dense opacities, two of which are well demonstrated in this tomographic cut (B 3/1. kansasii), were cultured from the sputum. Within a year the lesions healed.

468

CLINICAL

(or 72.4%) gave a relevant occupational history. Fifteen out of the 34 cases (or 44 %) showed radiologically associated pulmonary diseases (Table 2), the commonest was emphysema as described by Simon (1964) with due reference to lung size, cardiovascular changes and bullae. The nonkansasii group in this series is far too small to draw a comparison with the predominant M. kansasii, but in these few cases the resulting lesion appeared to be the same irrespective of the mycobacterium isolated (compare Figs. 2, 3). Although the criteria set for selection of patients were met in all 34 patients, these cases appear to fall into 2 groups: GROUO A. This group consisted of 32 patients where the lesion was localised and which we considered almost certainly had been produced by the opportunist mycobacteria. In 29 cases the lesion was restricted to one apex or to a segment of one upper lobe and in the remaining three both apices were involved. The r,adiological findings are summarised in Table 2; from which it is

FIG. 6 Postero-anterior radiograph of a 67-year-old bricklayer (Case 12) who was referred from the Rheumatology Clinic on account of cough which was present for two years. There is extensive shadowing throughout the left lung, mainly due to fibrosis. Lung scan showed very little perfusion, and drill biopsy was negative. Photochromogens speeiated as M. kansasii were isolated. Obviously these mycobacteria colonised the already damaged lung.

RADIOLOGY

obvious that this is usually a cavitary disease. Often a single cavity of about 2-5 cm in diameter was present, although in some cases it was bigger. A few cases presented with several small cavities grouped together in the apical segment (Fig. 4). Such cavities, whether single or multiple, rarely presented with a very thick wall, often they were thin-walled. Infiltration around cavities was minimal or absent. Pleural thickening, calcification and bronchogenic spread were rare. Four cases showed a distinctive appearance as described by Cook, Riddell and Simon (1971). This consisted of irregular opacities, grouped around central transradiant areas, with tail-like linear shadows radiating towards the periphery. One of these four cases (Fig. 5) presented such an appearance together with cavities. Most of the lesions healed by fibrosis during the period of treatment and observation. GRouP B. Two patients (Cases 12 and 24) showed widespread pre-existing pulmonary disease (Fig. 6). In these cases the opportunist mycobacterium behaved as a saprophyte by colonisation of the already damaged lung, with minimal further damage. No extrapulmonary lesions, osseous or lymphatic, as reported by Heitzman and his colleagues (1968) were seen in this series. CONCLUSIONS In general the presenting symptoms were not materially different from those found in sufferers from pulmonary tuberculosis. By far the commonest non-tuberculous mycobacterium to cause infection was found to be the M. kansasii. Pre-existing or associated pulmonary disease was common. In most cases the lesion was cavitary and spread to other parts of the lung was rare. Healing took place by fibrosis with minimal pleural reaction or calcification. The typical radiological appearances are not pathognomonic, and bacteriological investigation is necessary to confirm the disease. When treated with appropriate chemotherapy as indicated by sensitivity tests, healing took place with cavity shrinkage and the disappearance from the sputum of the mycobacterium, sometimes within three months from the commencement of the treatment.

Acknowledgements. - We thank Dr J. Marks for confirmation of identity and sensitivity testing of some of the mycobacteria included. We are also grateful to Miss T. Storey and Miss S. Tingle for their secretarial assistance.

P U L M O N A R Y LESIONS DUE TO O P P O R T U N I S T M Y C O B A C T E R I A REFERENCES CHAPMAN, J. S. (1962). The present status of the unclassified mycobacteria. American Journal of Medicine, 33, 471. COLLINS, C. H. (1962). The classification of 'Anonymous' acid-fast bacilli from human sources. Tubercle, 43, 292-298. CooK, P_ L., RIDDELL, R. W. & SI~ON, G. (1971). Bacteriological and radiological features of lung infection by opportunist mycobacteria: a review. Tubercle, 52, 232-241. HEITZMAN, E. R., BORNI-IURST, R. A. & RUSSELL, J. P. (1968). Disease due to anonymous mycobacteria - potential for specific diagnosis. American Journal of Roentgenology Radium Therapy and Nuclear Medicine, 103, 533-539. KELLER, R. H, & RUNYON, E. H. (1964). Mycobacterial diseases. American Journal of Roentgenology, 2, 528-539.

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MARKS, J. (1969). Opportunist mycobacteria in England. Wales. Tubercle, 50, Suppl., 78-80. MARKS, J. & JENKINS, P. A. (1971). The opportunist mycobacteria - a 20 year retrospect. Postgraduate Medical Journal, 47, 705-709. MARKS, J. & RICHaRDS, M. (1962). Classification of the anonymous mycobacteria as a guide to their significance.

Monthly Bulletin of the Ministry of Health and the Public Health Laboratory Service, 21, 200-208. RUNYON, E. H. (1959). Anonymous mycobacteria in pulmonary disease. Medical Clinics of North America, 43, 273-290. SEInERT, C. E. & TnnRISKY, J. (1969). Radiological features of pulmonary atypical mycobacterial infections. British Journal of Radiology, 42, 140-144. S~MON, G. (1964). Radiology and emphysema. Clinical Radiology, 15, 293-306.