Resph'atory Medicine (1992) 86, 345-347
Pulmonary alveolar-septal amyloidosis- an unusual radiographic presentation R. A. M O R G A N * ~ , N. J. RING* AND A. J. M A R S H A L L t
*X-ray Department and ~Department of Cardiology, Derriford Hospital, Plymouth, U.K.
Introduction Amyloid deposition in the respiratory system is common in systemic amyloidosis. Amyloid is laid down in the pulmonary interstitium and vasculature and is frequently found at post-mortem in patients who have succumbed to cardiac or renal involvement by amyloid. Amyloidosis initially localized to the respiratory tract, however, is rare. Amyloidosis of the respiratory tract occurs in three patterns: (1) a tracheo-bronchial form; (2) a macronodular form; and (3) alveolar-septal or interstitial form. Tracheo-bronchial amyloidosis is an indolent form of localized amyloidosis which may cause bronchial stenosis; it generally produces few symptoms but is often confused with malignancy or TB, especially when the nodules cavitate. Neither of the above forms is generally part of a systemic amyloidosis (I,2). Diffuse alveolar-septal amyloid is the least common form reported (3) and is associated with the systemic syndrome, progressive exertional dyspnoea and a poor prognosis.
Case Report A 60-year-old man with a history of asbestos exposure presented with a progressive exertional dyspnoea &recent onset. Benign monoclonal gammopathy had been diagnosed in 1982. The patient smoked infrequently. No other history of note. On examination, there were fine bilateral basal inspiratory crackles only. The initial chest radiograph was reported as normal but actually showed generalized small nodular infiltrates mainly in the lower zones [Plates l(a) and (b)]. Cardiac failure was diagnosed and the patient treated with diuretics. Six months later, he reported debilitating exertional dyspnoea, ankle swelling and orthopnoea. The chest Received 27 June 1991 and accepted in revised form 10 December 1991. +To whom correspondence should be addressed at: Department of Radiology, St Georges Hospital, Blackshaw Road, Tooting, London SWI7, U.K. 0954-6111/92/040345 + 03 $03.00/0
radiograph now showed, in addition to micronodular infiltrates, evidence of congestive cardiac failure with linear interstitial shadowing, septal lines and small bilateral pleural effusions, although the heart size remained at the upper limit of normal. Further medical treatment resulted in substantial clearing of the interstitial oedema and septal lines but with persistence of the nodular shadowing. Creatinine clearance was 70 ml min -~. Mantoux test was negative. Electrocardiography revealed low voltage but normal complexes. Echocardiography showed a thickened pericardium and a small pericardial effusion. The myocardium of both ventricles was thickened, echogenic and stiff. The LV wall motion was jerky and the ejection fraction was 68%. These findings were suggestive of a restrictive cardiomyopathy and this was confirmed by pressure studies at cardiac catheterization. The findings of a low voltage ECG, a thickened myocardium and restrictive cardiomyopathy suggested a diagnosis ofamyloidosis. This was confirmed by biopsy of the rectal mucosa and endocardium. The patient rapidly deteriorated and died within 6 months of referral. Subsequent histological examination of the lungs revealed amyloid deposits throughout the pulmonary vasculature and interstitium. Amyloid deposits were also found in the heart, liver, spleen and kidneys. No evidence of asbestos or pulmonary fibrosis was found.
Discussion The main features of this case are the development of symptomatic alveolar-septal pulmonary amyioidosis before the onset of systemic amyloidosis and the initial radiographic presentation with micronodular infiltrates rather than linear interstitial shadowing which is usually described. Involvement of the respiratory tract is common in systemic AL amyloidosis but only rarely in secondary AA amyloidosis. Only in a minority is it of clinical © 1992 Bailli6re Tindall
346
R. A . M o r g a n et al.
Plate I (a) Chest radiograph at presentation with micronodular shadowing. (b) Magnified view of left lower zone showing micronodular infiltrates.
significance as in our patient because the clinical findings are usually dominated by cardiac and renal involvement (1,4). Moreover, there are few reports of systemic AL amyloidosis presenting initially with lower respiratory tract disease. In a review of 144 cases of systemic amyloidosis, Janssen et al. found no patients presenting with amyloidosis localized to the lower respiratory tract (5). In our patient, amyloid deposits were located in the pulmonary vessels and interstitium. This agrees with the findings of Cordier et al. who suggested that the severity of the respiratory impairment largely depends on the degree to which the gas exchange zones are affected (I). Linear or reticular interstitial shadowing have been the most widely reported signs of diffuse alveolarseptal amyloidosis on the chest radiograph (1-8). Very much rarer are reports of micronodular infiltrates (nodules < 5 mm) as distinct from the larger nodules seen in localized macronodular amyloidosis. Cordier reported one patient with reticuio-nodular shadowing who had systemic amyloidosis with pulmonary involvement. Both the cases of alveolar-septal amyloidosis described by Road et al. and Gregoire et al. presented with linear interstitial shadowing on the chest radiograph (7,8). Neither author describes micronodular infiltrates as a feature in their reports. Gacouin et al.
reported a patient with diffuse pulmonary amyloid who presented with micronodular infiltrates. Most unusually he was still alive 6 years after the initial presentation (9). The differential diagnosis of micronodular infiltrates includes metastatic disease, miliary TB, sarcoidosis and occupational lung disease. These were all excluded either ante- or post-mortem. Micronodular shadowing may rarely be the sole manifestation of pulmonary oedema. In our patient micronodular shadowing predated the onset of other radioiogical signs of cardiac failure by several months. Moreover, following the development of septal lines, interstitial shadowing and pleural effusions, these cleared substantially with medical treatment, whereas the nodular shadowing did not. Based on the clinical, radiological and histological evidence, we have described a patient with systemic AL amyloidosis presenting with severe progressive exertional dyspnoea because of amyloid localized initially to the lower respiratory tract and micronodular rather than reticular shadowing on the chest radiograph.
Acknowledgement We are grateful to Karen Creed for the typing and to Sallie Waring and Trevor McCausland for their work in Medical Photography.
Pulmonary alveolar-septal amyloidosis References
1. Cordier JF, Loire R, Brune J. Amyloidosis of the lower respiratory tract. Chest 1986; 90:827-83 I. 2. Hui AN, Koss MN, Hochholzer L, Wehunt WD. Amyloidosis presenting in the lower respiratory tract: clinicopathologic; radiologic; immunohistochemical and histochemical studies on 48 cases. Arch Pathol Lab Med 1986; 110: 212-218. 3. Kanada TJ, Sharma OP. Long term survival with diffuse interstitial pulmonary amyloidosis. Am J Med 1979; 67: 879-882. 4. Gertz MA, Greipp PR. Clinical aspects of pulmonary amyloidosis. Chest 1986; 90:790-791. 5. Janssen S, Van Rijswijk MH, Meijer S, Ruinen L, Van Der Hem GK. Systemic amyloidosis: a clinical survey of 144 cases. Neth J Med 1988; 29: 376-385.
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6. Petermann W, Barth J, Schluter E. Localised amyloidosis of central airways. Eur J Respir Dis 1987; 71: 210-212. 7. Gregoire JM, Close P, Dourov N, Stoffels G. Pulmonary alveolo-septal amyloidosis. ACTA. Clinica Belgica 1986; 41: 388-394. 8. Road JD, Jacques J, Sparling JR. Diffuse alveoloseptal amyloidosis presenting with recurrent haemoptysis and medial dissection of the pulmonary arteries. Am Rev Respir Dis 1985; 132: 1368-1370. 9. Gacouin JC, Vaury Ph, Degos CF, Sauvaget J. Apropos d'une observation d'amylose pulmonaire diffuse associee a des signes neurologiques perepheriques. Review. Pneumologiques Clinics 1986; 42: 258-268.
Pulmonary alveolar-septal amyloidosis- an unusual radiographic presentation R. A. M O R G A N * ~ , N. J. RING* AND A. J. M A R S H A L L t
*X-ray Department and ~Department of Cardiology, Derriford Hospital, Plymouth, U.K.
Introduction Amyloid deposition in the respiratory system is common in systemic amyloidosis. Amyloid is laid down in the pulmonary interstitium and vasculature and is frequently found at post-mortem in patients who have succumbed to cardiac or renal involvement by amyloid. Amyloidosis initially localized to the respiratory tract, however, is rare. Amyloidosis of the respiratory tract occurs in three patterns: (1) a tracheo-bronchial form; (2) a macronodular form; and (3) alveolar-septal or interstitial form. Tracheo-bronchial amyloidosis is an indolent form of localized amyloidosis which may cause bronchial stenosis; it generally produces few symptoms but is often confused with malignancy or TB, especially when the nodules cavitate. Neither of the above forms is generally part of a systemic amyloidosis (I,2). Diffuse alveolar-septal amyloid is the least common form reported (3) and is associated with the systemic syndrome, progressive exertional dyspnoea and a poor prognosis.
Case Report A 60-year-old man with a history of asbestos exposure presented with a progressive exertional dyspnoea &recent onset. Benign monoclonal gammopathy had been diagnosed in 1982. The patient smoked infrequently. No other history of note. On examination, there were fine bilateral basal inspiratory crackles only. The initial chest radiograph was reported as normal but actually showed generalized small nodular infiltrates mainly in the lower zones [Plates l(a) and (b)]. Cardiac failure was diagnosed and the patient treated with diuretics. Six months later, he reported debilitating exertional dyspnoea, ankle swelling and orthopnoea. The chest Received 27 June 1991 and accepted in revised form 10 December 1991. +To whom correspondence should be addressed at: Department of Radiology, St Georges Hospital, Blackshaw Road, Tooting, London SWI7, U.K. 0954-6111/92/040345 + 03 $03.00/0
radiograph now showed, in addition to micronodular infiltrates, evidence of congestive cardiac failure with linear interstitial shadowing, septal lines and small bilateral pleural effusions, although the heart size remained at the upper limit of normal. Further medical treatment resulted in substantial clearing of the interstitial oedema and septal lines but with persistence of the nodular shadowing. Creatinine clearance was 70 ml min -~. Mantoux test was negative. Electrocardiography revealed low voltage but normal complexes. Echocardiography showed a thickened pericardium and a small pericardial effusion. The myocardium of both ventricles was thickened, echogenic and stiff. The LV wall motion was jerky and the ejection fraction was 68%. These findings were suggestive of a restrictive cardiomyopathy and this was confirmed by pressure studies at cardiac catheterization. The findings of a low voltage ECG, a thickened myocardium and restrictive cardiomyopathy suggested a diagnosis ofamyloidosis. This was confirmed by biopsy of the rectal mucosa and endocardium. The patient rapidly deteriorated and died within 6 months of referral. Subsequent histological examination of the lungs revealed amyloid deposits throughout the pulmonary vasculature and interstitium. Amyloid deposits were also found in the heart, liver, spleen and kidneys. No evidence of asbestos or pulmonary fibrosis was found.
Discussion The main features of this case are the development of symptomatic alveolar-septal pulmonary amyioidosis before the onset of systemic amyloidosis and the initial radiographic presentation with micronodular infiltrates rather than linear interstitial shadowing which is usually described. Involvement of the respiratory tract is common in systemic AL amyloidosis but only rarely in secondary AA amyloidosis. Only in a minority is it of clinical © 1992 Bailli6re Tindall
346
R. A . M o r g a n et al.
Plate I (a) Chest radiograph at presentation with micronodular shadowing. (b) Magnified view of left lower zone showing micronodular infiltrates.
significance as in our patient because the clinical findings are usually dominated by cardiac and renal involvement (1,4). Moreover, there are few reports of systemic AL amyloidosis presenting initially with lower respiratory tract disease. In a review of 144 cases of systemic amyloidosis, Janssen et al. found no patients presenting with amyloidosis localized to the lower respiratory tract (5). In our patient, amyloid deposits were located in the pulmonary vessels and interstitium. This agrees with the findings of Cordier et al. who suggested that the severity of the respiratory impairment largely depends on the degree to which the gas exchange zones are affected (I). Linear or reticular interstitial shadowing have been the most widely reported signs of diffuse alveolarseptal amyloidosis on the chest radiograph (1-8). Very much rarer are reports of micronodular infiltrates (nodules < 5 mm) as distinct from the larger nodules seen in localized macronodular amyloidosis. Cordier reported one patient with reticuio-nodular shadowing who had systemic amyloidosis with pulmonary involvement. Both the cases of alveolar-septal amyloidosis described by Road et al. and Gregoire et al. presented with linear interstitial shadowing on the chest radiograph (7,8). Neither author describes micronodular infiltrates as a feature in their reports. Gacouin et al.
reported a patient with diffuse pulmonary amyloid who presented with micronodular infiltrates. Most unusually he was still alive 6 years after the initial presentation (9). The differential diagnosis of micronodular infiltrates includes metastatic disease, miliary TB, sarcoidosis and occupational lung disease. These were all excluded either ante- or post-mortem. Micronodular shadowing may rarely be the sole manifestation of pulmonary oedema. In our patient micronodular shadowing predated the onset of other radioiogical signs of cardiac failure by several months. Moreover, following the development of septal lines, interstitial shadowing and pleural effusions, these cleared substantially with medical treatment, whereas the nodular shadowing did not. Based on the clinical, radiological and histological evidence, we have described a patient with systemic AL amyloidosis presenting with severe progressive exertional dyspnoea because of amyloid localized initially to the lower respiratory tract and micronodular rather than reticular shadowing on the chest radiograph.
Acknowledgement We are grateful to Karen Creed for the typing and to Sallie Waring and Trevor McCausland for their work in Medical Photography.
Pulmonary alveolar-septal amyloidosis References
1. Cordier JF, Loire R, Brune J. Amyloidosis of the lower respiratory tract. Chest 1986; 90:827-83 I. 2. Hui AN, Koss MN, Hochholzer L, Wehunt WD. Amyloidosis presenting in the lower respiratory tract: clinicopathologic; radiologic; immunohistochemical and histochemical studies on 48 cases. Arch Pathol Lab Med 1986; 110: 212-218. 3. Kanada TJ, Sharma OP. Long term survival with diffuse interstitial pulmonary amyloidosis. Am J Med 1979; 67: 879-882. 4. Gertz MA, Greipp PR. Clinical aspects of pulmonary amyloidosis. Chest 1986; 90:790-791. 5. Janssen S, Van Rijswijk MH, Meijer S, Ruinen L, Van Der Hem GK. Systemic amyloidosis: a clinical survey of 144 cases. Neth J Med 1988; 29: 376-385.
347
6. Petermann W, Barth J, Schluter E. Localised amyloidosis of central airways. Eur J Respir Dis 1987; 71: 210-212. 7. Gregoire JM, Close P, Dourov N, Stoffels G. Pulmonary alveolo-septal amyloidosis. ACTA. Clinica Belgica 1986; 41: 388-394. 8. Road JD, Jacques J, Sparling JR. Diffuse alveoloseptal amyloidosis presenting with recurrent haemoptysis and medial dissection of the pulmonary arteries. Am Rev Respir Dis 1985; 132: 1368-1370. 9. Gacouin JC, Vaury Ph, Degos CF, Sauvaget J. Apropos d'une observation d'amylose pulmonaire diffuse associee a des signes neurologiques perepheriques. Review. Pneumologiques Clinics 1986; 42: 258-268.
