Pulmonary Manifestations of Collagen Diseases

Pulmonary Manifestations of Collagen Diseases

Pulmonary Manifestations of Collagen Diseases LYLE A. BAKER, M.D., F.A.C.P.* DOUGLAS DAVID, M.D.** fundamental characteristic of the "so-called" coll...

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Pulmonary Manifestations of Collagen Diseases LYLE A. BAKER, M.D., F.A.C.P.* DOUGLAS DAVID, M.D.**

fundamental characteristic of the "so-called" collagen diseases, which have occupied such a prominent place in medical discussion in recent years, is their widely diversified and variable clinical manifestations. Pulmonary manifestations have been described not infrequently, but have attracted much less attention than involvements of other organs. Pulmonary involvement has been found to be more frequent and of greater magnitude in some of these entities than in others. It is also difficult or impossible to determine at times whether such involvement is a part of the disease per se or is a complication. Certainly, patients following a chronic course with any of the collagen diseases are subject to all of the pulmonary complications to which sufferers of chronic debility are heir. Bronchitis, bronchopneumonia, pulmonary embolism and congestion are not uncommon. Whether these conditions are intercurrent or part of the disease is difficult to determine even at autopsy. For this reason alone many of the conflicting concepts in the literature are understandable. In this discussion we shall limit ourselves to those clinical conditions which are generally accepted as belonging to the "collagen diseases." These are polyarteritis nodosa, disseminated lupus erythematosus, scleroderma and dermatomyositis. 1'he accumulated information on pulmonary involvement in each of these will be concisely presented.

THE

POLYARTERITIS NODOSA

Pulmonary manifestations have received more emphasis in polyarteritis nodosa than in the other collagen diseases. The striking and severe bronchial asthma which has been occasionally seen has served to

* Chief, Medical Service, Veterans Administration Hospital, I-l~nes, Illinois; Associate Clinical Professor of Medicine, University of Illinois College of Medicine. ** Chief, Cardiopulmonary Laboratory, Veterans Administration Hospital, Hines Illinois; Clinical Instructor in Medicine, University of Illinois College of Medicine. 145

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direct attention to the lungs in this condition. Rackemann and Green64 in 1939 found 19 cases in the literature, and added eight of their own in which polyarteritis and bronchial asthma were associated. They suggested the triad of severe bronchial asthma, eosinophilia and peripheral neuritis as being very suggestive of periarteritis nodosa. Wilson and Alexander 74 in a later review found this association existed in 18 per cent of the reported cases of polyarteritis nodosa. They believed the asthma to be of nonatopic or intrinsic type, and that the existing hypersensitivity could be responsible for irreversible vascular changes. This incidence of bronchial asthma has been one of the important factors in stimulating the theory that hypersensitivity plays a role in polyarteritis nodosa. Clinical symptoms related to the pulmonary system are common in this disease. Cough, sputum, shortness of breath, hemoptysis and pleuritic pains may be present. Pneumonia, usually of a disseminated patchy type, is not infrequent. Pleural effusion and even emphysema have occurred. Bronchiectasis with emphysema has also been present, but it is not likely that these conditions are related to polyarteritis nodosa. Chest pain may be a prominent symptom; the exact cause may be obscure and variable. While symptoms and findings referable to the respiratory tract are quite common, they are usually overshadowed by more severe manifestations ,of other tissues involved. Bronchial asthma is the exception. This usually has an onset before 40 years of age. It is severe and progressivQ and is frequently the major disabling factor. X-ray examination of the chest often reveals abnormal findings, but these are not peculiar to or diagnostic of polyarteritis. Conglomerate areas of density may be seen which tend to migrate from one area to another. Typical bronchopneu·monia or lobar pneumonia may be seen and pleural reactions are common. Herrmann32 has described in detail the pulmonary roentgen findings in one case. There was a diffuse perivascular infiltration which spread out from the hila with the formation of confluent opacities of moderate density. The involvement tended to be transient and variable. Final termination was manifested by pulmonary infarcts with bilateral pleural effusion. At autopsy, characteristic pathological findings were present in both bronchial and pulmonary arteries. Garland and Sisson21 describe patchy nodular densities which are designated as pulmonary hives. Pulmonary linear markings may be accentuated, and edema may also be evident. Pulmonary cavitation has been reported by Sandler. 59 Pulmonary abscess formation due to polyarteritis has been demonstrated. 65 The pulmonary signs of associated emphysema and bronchiectasis have been noted. It must be emphasized that the x-ray findings are not diagno~tic of this condition. Rubin57 states that the nearest approach to a classical picture of polyarteritis nodosa is one of nodules of various size located principally in the mid or inner portions of the lung fields with emphysema of the sur-

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Fig. 33. Polyarteritis nodosa confirmed at necropsy. X-ray of the chest shows nodular and linear infiltrates at both lung bases and parahilar infiltrates bilaterally. The minor fissure is thickened. There is evidence of residual opaque material at both bases.

rounding parenchyma. Another fairly characteristic appearance is the "butterfly" distribution of dense irregular infiltrations. It is to be pointed out that while abnormal x-ray findings in the chest are common in this disease, these are not usually of a specific type which would suggest the clinical diagnosis. While clinical symptoms and signs of a pulmonary nature are quite common, having been reported as occurring in from 47 to 85 per cent of cases, the demonstration of lesions in the vasculature of the lungs is less frequent. Har,ris et a1. 29 reported lesions in the pulmonary vessels in 25 per cent ·of patients with polyarteritis nodosa. Sweeney and Baggenstoss 62 found vascular lesions in seven of 28 cases examined. These vascular lesions found have varied in severity, but all have inflammatory characteristics. There may be a vasculitis with thickening of the walls, or the process may be more severe, resulting in necrotizing lesions ofthe vessels. In some cases aneurysmal formation has been noted. Zeek 75 believes that the pulmonary 'arteries are involved only when pulmonary hypertension is present. The bronchial arteries are much more frequently affected. Ellman and Cudkowicz 16 also stressed the involvement of the latter and believe the pulmonary changes are due to the resultant progressive ischemia. Sweeney and. Baggenstoss 62 found that the pulmonary arterioles more frequently show. pathological changes. Zeek 76 found the pulmonary vessels to be much more frequently affected in the group of cases classified as "hypersensitivity" arteritis than in the classical polyarteritis nodosa. Parenchymal lung lesions due to polyarteritis have been described.

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Ophuls,50 in 1923, reported histological involvement of the pulmonary vessels associated with infiltration of the pulmonary parenchyma. Small disseminated granulomatous areas which sometimes break down into abscess formation may occur. Areas of necrotizing pneumonitis have been observed. There may be thickening of the alveolar septa and fibrinoid changes in the alveolar membranes. Extensive destruction and cavitation throughout all lobes with bronchiectasis were reported by Sweeney and Baggenstoss. 62 While many of the pulmonary findings in the course of polyarteritis are coincidental, it is evident that such occurrences may be manifestations of the disease itself. Both Wiener 73 and Weir 71 have described the miliary foci of organizing pneumonia with cellular infiltration and local eosinophilia. This is thought to be characteristic of polyarteritis. This occurs most prominently in the hilar areas and lower lobes. There is one question regarding the relationship of polyarteritis to the pulmonary circulation which is quite puzzling. There are several well authenticated reports of lesions characteristic of polyarteritis which were found to be confined to the pulmonary circulation. Old and Russe1l 47 report a case of Eisenmenger's complex in which lesions typical of periarteritis were found confined to the pulmonary arteries at autopsy. All the classical stages of lesions from acute to healed were present. I{ipkie and Johnson36 reported two cases, one of Eisenmenger's complex and one of glomerulonephritis, in which the lesions were also confined to the pulmonary arteries. They suggested that hypertension within the vasculature is a primary factor in the etiology of these lesions. McKeown44 reported cases designated as "primary pulmonary hypertension" with periarteritis confined to the pulmonary arteries. Symmers 63 discusses the pathological characteristics of the lesions noted in two cases, one of primary pulmonary hypertension and the other mitral stenosis. He pointed out that some lesions were typical of periarteritis nodosa, others resembled those found in benign systemic hypertension. He also noted necrotizing lesions similar to those seen in malignant hypertension. This author cites another case report of mitral stenosis which revealed periarteritis lesions confined to the pulmonary arteries. Symmers agrees with Kipkie and Johnson 36 that the arterial lesions are the result of hypertension and not the cause. Braunstein 7 discusses polyarteritis nodosa limited to the pulmonary circulation in six cases. There was pulmonary hypertension in all patients. The pulmonary arteries were chiefly affected, which confirms the opinion of Zeek. 75 It is apparent that polyarteritis limited to the pulmonary circulation is nearly always found in association with pulmonary hypertension. The etiology of this hypertension is variable. McKeown 44 has reported four patients with primary pulmonary hypertension who revealed at autopsy lesions typical of periarteritis nodosa. These lesions were limited to the lungs. Whether such cases can properly be considered as polyarteritis nodosa

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in the conventional clinical concept is questionable. In fact, the existence of polyarteritis in any form as a primary clinical entity is subject to doubt. The presentation of Zeek~76 and Knowles at al. 38 of the classification of "necrotizing angiitis" has not made for a simple conclusion. In accordance with this classification, direct involvement of the vessels of the lungs is quite rare in periarteritis nodosa. These vessels are frequently involved in "hypersensitivity angiitis." DISSEMINATED LUPUS ERYTHEMATOSUS

Since disseminated lupus is a condition with a well known predilection for the serous surfaces of the body, it is to be expected that the pleural surfaces would be a frequent source of clinical symptoms. Pleurisy with or without effusion occurs commonly at some time during the course of this disease. The combination of pericarditis with pleurisy has long been regarded as one of the signal clinical characteristics of this disease. Intermittent acute symptoms from inflammatory pleural lesions may precede other diagnostic manifestations by months or years. 14 Involvement of the lung parenchyma has received considerable attention during recent years. Rakov and Taylor55 in 1942 called attention to this pulmonary pathology. The lungs showed lobular consolidation. This area sometimes was a solid inflammatory mass with no lung architecture remaining. In some consolidated areas there was a diffuse invasion of inflammatory cells with thickening of the alveolar septi. These authors stressed the fact that parenchymallung involvement was not uncommon in disseminated lupus erythematosus. Casual mention of the observation of migratory lobular consolidation in the lung fields had been made by both Osler5! and Tremaine 68 in previous articles. Klemperer et al.,37 in discussing the clinical manifestations of this disease, stressed the occurrence of long-continued bouts of waxing and waning bronchopneumonia as being characteristic. These authors believed that the clinical manifestations were far more impressive than indicated by the pathological findings. Reifenstein et a1. 56 also noted that pulmonary involvement may be persistent over many months in such patients. Foldes19 has described the pulmonary changes in acute systemic lupus erythematosus. Atelectatic bronchopneumonia was a typical finding, usually of a scattered patchy segmental type. Also suppurative bronchitis may be present. He also called attention to a suppurative angiitis with typical fibrinoid changes in the blood vessels. These alterations may on occasion lead to severe impairment of pulmonary function. Baggenstoss 3 described mucinous deposits in the interstitial tissue of the lungs. He believed these changes may be a precursor of interstitial pneumonitis. These observations support the view that the lungs may be involved as a fairly typical aspect of the disease itself. In relation to this

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point, Teilum 66 has described focal disseminated areas of what he designates as allergic pneumonitis. These are most pronounced just beneath the pleura. l"here is accompanying fibrinoid degeneration of the alveolar walls and at times necrosis. Fibrosis may result from healing, and also small granulomas may occur. He also describes vascular changes which he considers of allergic character. He believes this type of pneumonia to be of specific pathological character. l'hore1l 67 remarks on the pleuritic involvement in association with the patchy (subpleural) pneumonia or atelectasis as being sufficient to suggest the presence of disseminated lupus. Tumulty 69 indicates that the pulmonary manifestations due to lupus not infrequently go unrecognized and are interpreted as being those of complicating infection. Purnell et al.,53 in a review of the autopsy findings in a series of 54 patients with lupus erythematosus, noted that over half had evidence of pulmonary disease. The nature of this disease was variable from congestion through bronchopneumonia and interstitial pneumonia. Pleural effusion was common. All observers agree that clinical manifestations of pulmonary origin ate common and expected during the course of disseminated lupus erythematosus. Griffith and Vural27 found jn a review of 18 cases that cough, dyspnea, chest pains and occasional hemoptysis were common symptoms. Of the 18 patients, 16 showed evidenc(~ of pulmonary disease at some time during their clinical course. Bille 6 found that 10 of 15 patients revealed x-ray evidence of pulmonary and pleural involvement. Jessar et al.,35 in an analysis of a large series of cases of this disease, found that pulmonary manifestations were present at some time in 38 per cent of the patients. While pleural findings were most frequent, parenchymal involvement was not uncommon. Israe134 discussed the pulmonary manifestations in this disease in 1953. He found that in a series of 22 cases the lungs or pleura were affected in 20 patients. Pneumonia was the most frequent clinical finding, 15 of the patients having such evidence on one or more occasions. The pneumonia was usually of a patchy distribution, though lobar involvement did occur. He points out that the presenting aspect of the disease may be pulmonary in character. He groups the pulmonary manifestations into three clinical types; recurrent episodes of pneumonia, those simulating pulmonary tuberculosis, and those with symptoms predominantly respiratory. Among nine autopsies in this group of patients, no characteristic pulmonary arterial lesions were found. It was Israel's conjecture that the disease may cause some alteration in bronchial or pulmonary structure which predisposes to pulmonary infection. This concept implies that the pulmonary findings are not a direct manifestation of the disease itself. The tendency for pneumonia to recur over long periods of time is emphasized by the case report of Hodges,33 which spanned a period of four years.

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Harvey et a1. 32 in a comprehensive review describes the clinical symptomatology in detail. Cough may be persistent, hacking in character and very exhausting. Usually there is little sputum. There may be streaking or frank hemoptysis. Tachypnea and dyspnea are common. Cyanosis may be present which is unrelieved by oxygen. Chest distress of various types occurs commonly. These authors remark on the paucity of physical findings in some patients in whom x-ray reveals definite abnormality. These observations tend to coincide with those of Foldes 19 and Teilum 66 with respect to the pathological findings in the lungs. Hyaline thickening and necrosis of the alveolar membranes, interstitial pneumonia with hemorrhage and atelectasis, and capillary thrombi were noted. In an analysis of 105 cases of disseminated lupus erythematosus, these authors found that 46 had various types of pulmonary involvement. They believed that the changes in 20 of these 46 patients were due to the disease. Lesions in the alveoli of the lungs similar to the "wire-loop" lesions of the kidney in disseminated lupus are described by Cluxton. ll It is quite apparent that pulmonary symptoms and findings are outstanding in the clinical manifestations of this disease. There is adequate evidence for believing that pulmonary lesions may be part and parcel of the disease. On the other hand, secondary infection and other factors also are prominent in bringing about pulmonary changes. It is often difficult or impossible to determine clinically to what extent such changes are directly due to disseminated lupus. SCLERODERMA (PROGRESSIVE SYSTEMIC SCLEROSIS)

Pathological changes in the lungs have been delineated more distinctly in scleroderma than in other "collagen diseases." As early as 1895 the pulmonary aspects of this disease were reported by Levine and Heller. 40 After having discussed the clinical pulmonary manifestations of scleroderma in 1889,17 Finlay in 1891 18 described pulmonary fibrosis as one facet of the widespread systemic character of scleroderma. Matsui43 described the autopsy findings of pulmonary fibrosis in patients with scleroderma. It is evident that for a long time pulmonary involvement has been considered to be an element of progressive systemic sclerosis which makes up the clinical entity of saleroderma. Garland and Sisson22 have recently classified the x-ray manifestations of scleroderma as follows: Ca) diffuse or localized fibrosis; (b) diffuse or localized nodulation; Cc) subpleural cystic disease, and Cd) calcification. The roentgenological characteristics of pulmonary fibrosis occurring in scleroderma were described by Murphy et a1. 45 in 1941. Later Hayman and Hunt 31 discussed this subject in detail in a review of 28 cases showing x-ray evidence of lung disease due to scleroderma. Shuford et al. 60 in a review of 37 cases of clinically established scleroderma found five in which abnormal chest x-ray findings were present. They describe this as

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Fig. 34. Progressive systemic sclerosis confirmed at necropsy. X-ray reveals pleural thickening at the right base. Also, there are linear and fine granular infiltrates at both lung bases. Cardiomegaly is present.

a widespread linear reticulated infiltration most marked in the lower half of the lung fields. Pugh et al. 62 state that the x-ray appearance of pulmonary scleroderma is rather distinctive but that description is inadequate. Hayman and Hunt31 noted a general similarity in the x-ray findings in all cases. Early there was a slight diffuse mottling of interlacing linear shadows in the lower two-thirds of the lung fields. With time this became a diffuse netlike shadow. Occasionally there were definite cystic formations. The cardiac and diaphragm contours were often irregular. These descriptive findings are identical with those first described by Murphy et al. 46 in 1941. Harper28 adds that recurrent patchy pneumonitis may be seen. This is frequently associated with x-ray evidence of pleurisy, some with effusion. It is of interest that Church and Ellis10 reported that iodized oil instilled into the bronchi did not appear to enter any of the cysts. Both Hayman and Hunt,31 as well as Murphy et al.,45 also report bronchography as being essentially normal. The pathology in scleroderma, as in the other diseases of the "collagen group," is a fundamental disturbance of the connective tissue. According to Duff,16 there are three characteristics' of the pathology: fibrinoid necrosis, proliferation of dense connective tissue, and the inflammatory reaction to the connective tissue injury. The proliferation of dense connective tissue is far more prominent than the other two, hence the essential finding in the lungs is progressive pulmonary fibrosis of varying degree. This is usually a linear diffuse fibrosis involving the lower lung fields bilaterally. The usual alteration, according to Hayman and Hunt, is a sclerosing alteration in the collagen framework of the lung. This

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causes stiffening of the lung, and there may be considerable thickening of the alveolar walls. Harper28 has suggested that such fibrosis might result from aspiration due to the malfunctioning of the esophagus. While this factor may operate to a limited extent, the consensus regards the pulmonary fibrosis as related to the generalized sclerosis characteristic of scleroderma. Getzowa23 discussed in an interesting manner the pathology of pulmonary scleroderma under two headings: cystic sclerosis of the lung, and compact pulmonary sclerosis. The first consists of multiple small cystic formations in the subpleural areas of the lower and central lobes. of the lungs. The author believes there occurs first the hyaline changes in the lung parenchyma which is followed by diffuse fibrosis of the alveolar walls and disappearance of the capillaries. Later in this fibrotic process degenerative changes occur with disappearance of alveolar walls, leaving behind the cystic structure. These cystic changes are not difSsimilar to those sometimes noted in influenzal pneumonia or pertussis. However, Getzowa points out that in these conditions the diffuse fibrotic process is not present. Dostrovsky13 confirms the pathological findings of Getzowa regarding cystic sclerosis. The author believes that the connective tissue is first involved, later the elastic tissue, and last the blood vessels. The view is expressed that cystic degeneration is a direct manifestation of scleroderma. Church and Ellis10 confirmed the presence of cystic fibrosis of the lung in scleroderma with the report of two cases. Spain and Thomas 61 expressed a different concept with respect to the evolution of this condition. They believe the cysts are actually due to emphysema secondary to obstruction due to peribronchial obstruction. These authors stress the associated presence of bronchiectasis. They believe that the musculoelastic coats of the bronchi are disrupted by the disease, predisposing to dilatation and bronchiectasis. The compact pulmonary sclerosis described by Getzowa23 consists of a progressive dense proliferation of fibrous tissue with disappearance of blood vessels and parenchymal architecture, leaving only solid fibrous connective tissue. Fibrinoid changes which caused marked obstructive symptoms 64 consistent with scleroderma have been noted in the bronchial mucosa. Involvement of the pulmonary blood vessels in scleroderma is infrequently mentioned. Weiss et a!. 72 described thickening of the walls of the pulmonary arteries with narrowing of the lumen. Bevans6 mentions that small arteries may be obliterated. Spain et a!. 61 as well as Goetz 24 have also called attention to the narrowing of the lumen of the small pulmonary arteries. Matsui43 referred to the disturbance in the pulmonary circulation with resulting right ventricular hypertrophy. While the capillary circulation may be considerably disrupted, it is apparent that extensive interference with the larger pulmonary arteries is uncommon. From this

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fact it would be expected that significant pulmonary hypertension and therefore cor pulmonale would be relatively uncommon. This supposition is supported by our present knowledge. Symptoms referable to the lungs are not uncommon in the course of scleroderma. Shortness of breath of some degree is frequent and may be severe in advanced cases. Cough is usually unproductive unless bronchiectasis is present. Cyanosis may be present if there is marked impairment of respiratory function. Weakness and fatigability are prominent when there is extensive pulmonary involvement. Hemoptysis is quite rare, and Hayman and Hunt31 report this symptom in only one case. Fever may be present, though this is not the rule. Weight loss is common. Clubbing of the fingers has been noted on occasion. In general, pulmonary symptoms do not appear until relatively late in the course of the disease. Usually skin manifestations with or without Raynaud's syndrome antedate such symptoms by a considerable period. Exceptions do occur in which both x-ray findings and symptoms precede the skin manifestations. It is also characteristic of scleroderma that not infrequently pulmonary symptoms are surprisingly absent or mild in the presence of marked x-ray evidence of lung involvement. On occasion pulmonary incapacity may be extreme. This may be dependent largely on interference with oxygen diffusion due to extensive thickening of the alveolar walls. This defect has been demonstrated by Spain and Thomas,61 and also in the case reported by Fox. 20 The marked interference which may be imposed on the respiratory mechanics by this disease cannot be ignored. In some patients, involvement of thoracic musculature and the diaphragm may lead to marked restriction of ventilatory capacity. Some attention has been paid in the literature to the heart in relation to scleroderma. Weiss et al., 72 in 1943, first clearly defined the fact that the heart was at times directly implicated in the classical pathological connective tissue alterations of scleroderma. Since then several authors have described the typical myocardial changes. 42 , 46, 26 These comprise usually a diffuse patchy collagenous fibrosis invading and replacing myocardial tissue. The coronary vessels are remarkably normal. Both the pericardium and endocardium may show similar changes. That there does occur on occasion "scleroderma heart disease" as an integral part of scleroderma is generally accepted. Impairment of cardiac function (cor pulmonale) caused by the pulmonary involvement in scleroderma is less common. Both Matsui43 and Kraus 39 recorded the finding of right ventricular hypertrophy at autopsy in the presence of pulmonary changes. It seems that one case of the series reported by Weiss et al. 72 (Case 4) could be so classified. That cor pulmonale is relatively rare when secondary to scleroderma involving the lungs is attested by the fact that among the 27 cases reviewed by Hayman and Hunt,31 right heart failure developed in only

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two. Shuford et aI.,60 in a series of 37 cases of scleroderma, found no clinically recognized cor pulmonale; however, this diagnosis was made at autopsy in one of these cases. In the series of 56 cases reviewed by Mahrer et al.,41 two patients died of congestive heart failure. These patients showed right ventricular hypertrophy, right heart failure, and indications of pulmonary hypertension. In another case, right axis deviation of the electrocardiogram was associated with enlargement of the pulmonary artery. In one of the three cases of scleroderma heart disease reported by Goetz,25 there was hypertrophy of the right ventricle alone. Though Goetz made no point of this finding, it is possible this might have been due to pulmonary hypertension. He does indicate that the chest x-ray was normal, which challenges this assumption. In studying the effects of pulmonary fibrosis on the heart, Baldwin et al. 4 reported findings on one case of scleroderma. Pulmonary hypertension was recorded, and the patient succumbed to right heart failure. Hypertrophy and dilatations of the right ventricle were found at postmortem examination. It is evident that cor pulmonale can occur as a result of lung disease due to scleroderma. It is likely that, as more careful investigation is made in the future, more such instances will be discovered. DERMATOMYOSITIS

Dermatomyositis is a rare disease of multiform character. The chief anatomic features of this disease are a nonsuppurative inflammation and degeneration of many muscles or the entire skeletal musculature. The condition may set in acutely, with severe and rapidly progressive symptoms, or it may appear in chronic form, with mild symptoms and sometimes with complete or partial remissions. The onset may be heralded by muscular, cutaneous or vasomotor signs. The upper respiratory passages, the bronchi and the lungs may be involved, with dyspnea, hoarseness or an alteration in the pitch of the voice. Involvement of the intercostal muscles may contribute to the decreased efficiency of the lungs as measured by a diminution in vital capacity.49 Pleural effusion has also been reported. The salient microscopic features in the diaphragm, pharyngeal and intercostal muscles comprise parenchymal and interstitial changes of nonspecific character and varying degree. These consist of fragmentation of fibers, granular, fibrinous and vacuolar degeneration, basophilic metachromasia and proliferation of nuclei in the muscle cells. At times, replacement by fibrosis supervenes prominently in myositis of long duration. Implication of certain striated muscles (that of the pharynx and the larynx, the intercostal muscles and the diaphragm) is an extremely serious complication of dermatomyositis. As functional evidence of the

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Fig. 35. Dermatomyositis confirmed at necropsy. Posteroanterior radiograph of the chest shows linear and nodular infiltrates at both lung bases.

underlying pathology is manifested, the hazard of bronchopneumonia increases. 8 Fluoroscopic examination of the chest may show diminished expansion of the lungs and reduced excursion of the diaphragm. X-ray study of the lungs may reveal interstitial infiltration or diffuse fibrosis. 66 O'Leary and Waisman49 reported·dyspnea in 10 of 40 patients and the vital capacity of two of them was found to be less than half the normal volume. They found dysphagia to bea symptom in 27 of 40 of their patients. The causes of death in 10 cases were as follows: (1) bronchopneumonia in six patients; (2) respiratory paralysis in three patients; and (3) cardiac failure in one patient. Caldwell and Aitchison 9 reported a case of dermatomyositis in which the expansion of the chest was severely restricted. The inspiratory capacity was reduced but the pulmonary mixing index, residual volume and functional residual capacity was normal. X-ray screening of the chest and cardiac catheterization revealed pulmonary hypertension and hypertrophy of the right heart, which they concluded were the result of degen.. erative and occlusive changes in the smaller branches of the pulmonary artery. The cause of death.before the antibiotic era was attributed frequently to an overwhelming infection. Infection is likely to be a serious problem at the present time, if there is weakness or paralysis of the pharyngeal and intercostal muscles which permits aspiration of products of digestion and the development of pneumonia. Cardiac failure from myocarditis may lead to death,70 as may pulmonary insufficiency caused by progressive fibrosis.

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PULMONARY FUNCTION TESTS

Pulmonary function studies in general have little diagnostic value in the study of collagen diseases. Even though the lung is neither the most frequent site of involvement nor the major focus of any collagen disease, a review of the pulmonary physiological data encountered in this group of diseases is indicated. As is the rule with most collagen diseases, physiologic data about the lungs are sparse or lacking in systemic lupus erythematosus. Andersen and Moersch1 report the studies of pulmonary function on one patient who had this disease with a diffuse pulmonary process. Studies of pulmonary function showed marked expiratory slowing. The residual volume was increased, but the total lung volume was decreased. The maximum breathing capacity was 18 per cent of estimated normal, and the vital capacity was 28 per cent of expected normal. Moderate arterial oxygen desaturation was present at rest and during exercise. The findings were indicative of pulmonary fibrosis associated with some degree of obstructive emphysema. Ellman and Cudkowicz 16 reported a case of lupus erythematosus in a patient who was dyspneic at rest with a shadow in the region of the left lower lobe, poor excursions of the left diaphragm and a vital capacity of 2 liters. Scleroderma may seriously disturb pulmonary function by restricting the expansion of the chest and lungs because of (1) thickening of the pleura by fibrosis; (2) increase of fibrous tissue in the skin and muscles of the chest wall; (3) thickening and fibrosis of the alveolar walls and the interalveolar septa; and (4) thickening and fibrosis of the intima of the arteries, thereby restricting the flow of blood through these vessels. Most authors,2, 12,58 measuring pulmonary function in scleroderma have found an abnormality in gas exchange across the alveolar-capillary membrane. Salomon and co-workers58 found no increase in the carbon dioxide tension or acid-base imbalance in the arterial blood. Their studies of arterial blood suggested difficulty with the exchange of oxygen. The widening of alveolar septa, thickening of blood vessel walls, and obliteration of vascular lumina cause a decrease in the pulmonary diffusing capacity. This consists of the resistance to diffusion through the pulmonary alveolar membrane, the pulmonary capillary wall and the effect of a reduced vascular bed. Measurements of pulmonary volume are the same as those of pulmonary fibrosis; that is, small values for the vital capacity and total lung capacity. The compliance of the lungs may be decreased as defined by less volume increase for the same change in pressure. The maximum breathing capacity may be normal or decreased, and an increase in residual volume with the latter is likely. Of course, with the above data one finds an increased residual volume/total lung capacity ratio. Arterial oxygen desaturation at rest or manifested by exercise is more likely to occur when the pulmonary diffusing capacity is decreased.

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Hypoxemia is due to changes in the pulmonary parenchyma, and decreased ventilatory ability results from the decreased expansion of the thoracic cage. In one of our patients vital capacity was markedly reduced, but there was no interference with air flow; on fluoroscopy there was decreased chest expansion, and arterial oxygen and carbon dioxide tensions were within normal limits at rest and at exercise. In our review of the literature we have not found physiologic studies of pulmonary function performed on patients ,vith proved periarteritis nodosa. Since the pulmonary manifestations of the disease are variable, one could expect the pulmonary function tests to differ markedly, depending on the type of pathology present. In dermatomyositis, muscle involvement may be a prominent or an insignificant clinical feature, but the muscle always shows microscopic changes. The degree of involvement is directly proportional to the stage of the disease. The ocular muscles, diaphragm, intercostals, and the muscles of the pharynx and larynx may be affected. Fluoroscopic examination of the chest may show diminished expansion of the lungs and reduced excursion of the diaphragm. Dyspnea and limitation of activity in patients with a collagen disease may be due to pulmonary insufficiency or myocardial insufficiency. A careful clinical history and physical examination including fluoroscopy of the chest usually permits a differential diagnosis of the etiology of the dyspnea and disability. Yet, not infrequently, disease of the heart and lung coexist and it becomes important to evaluate the relative contribution of each to the patient's total disability. Only after these relative values are ascertained is it possible to assess the effects on either of these components of any therapeutic regimen. SUMMARY

The pulmonary aspects of the various collagen diseases which have been reported in the literature have been reviewed. It is apparent that, with the exception of dermatomyositis, some type of pulmonary involvement is almost certain to occur at some time during the course of the diseases. Occasionally this may be the initiating or major clinical manifestation. An outstanding characteristic of the collagen diseases is the wide variety of pulmonary manifestations which have been noted. These vary widely from case to case and, even in the same patient, from time to time. In general, the pulmonary findings are nonspecific and of little diagnostic value. Perhaps only in scleroderma is the x-ray evidence sufficiently characteristic to lead to the diagnosis. It is difficult to differentiate between the pulmonary manifestations which are an integral part of the disease and those which are due to complicating infection. REFERENCES 1. Andersen, H. A. and Moersch, H. J.: Pulmonary Manifestations of Collagen Diseases. In: Gordon, B. L.: Clinical Cardiopulmonary Physiology. New York, Grune & Stratton, 1957, p. 384.

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