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Radiological observations on 33 cases of primary interstitial myocarditis during an outbreak in the Haifa area
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Radiological Observations on 33 Cases of Primary Interstitial Myocarditis during an Outbreak in the Haifa Area J. M U N K , M.D., ANn K. T. LEDERER, M.D.
X-ray Department, Rambam Government 1-32fs}ital, Haifa, lsrael OUT of 61 cases of primary interstitial myocarditis (idiopathic myocarditis) in children in the age-group between 6 months and 3½ years, which occurred in the Haifa area between May, 1956, and D e c e m b e r , 1957, 33 were radiographed (z8 in this hospital and 5 in the Rothschild Hospital, Haifa). Fifty of the children died and in all these, except one, the diagnosis was confirmed by p o s t - m o r t e m examination ; I I children survived. T h e 28 children who died without previous X - r a y examination arrived at the hospital either in extremis or already deceased. F r o m the clinical as well as from the epidemiological point of view the occurrence of the cases showed the characteristics of an epidemic outbreak and was described as such (Freundlieh, Berkowitz, Elkon, and Wilder, 1958). T h e y report on 57 cases. I n our paper 4 additional cases are included. T h e s e 4 children survived. T h e y presented radiological features which we considered typical of the disease. Primary interstitial myoearditis was first described by Fiedler (19oo) in an adult and by Z u p p i n g e r (19Ol) in a child. Since then reports On small groups of cases have appeared in the literature from various parts of the world. T h e greatest n u m b e r of cases described (14o) occurred in M u n i c h during the years 1937-44 (Stoeber, 1952). In recent years, however, several outbreaks of epidemic character were reported : one comprising IO cases was reported from a maternity h o m e in Johannesburg (Javett, H e y m a n n , M u n d e l , Pepler, Lurie, Gear, Measrock, and Kirsch, 1956), a further outbreak of 9 cases in a maternity h o m e in Southern Rhodesia (Montgomery, Gear, Prinsloo, Kahn, and Kirsch, I955) , 4 cases in A m s t e r d a m (van Creveld and Jager, I956), and 8 cases in Athens reported by Choremis, Cassimos, Nikoyannopoulos, Mavrou, and Haka (1956). T h e main features of this outbreak in the Haifa area were t h a t : - I. Within a period of 20 months 6I cases occurred in the relatively small Haifa district, while f r o m other parts of the country no increase above the usual n u m b e r of cases ( i - 2 a year in each of the big hospitals) was reported, which points in favour of the epidemic character of the occurrence. 2. Eleven out of 27 patients who died in 1957 showed histopathological evidence of diffuse interstitial pneumonia in addition to typical pathological signs of primary interstitial myocarditis, 3. Eight out of the 27 patients who died in 1957 presented on histopathological examination in addition to signs of interstitial myocarditis areas of subendocardial fibrosis (Gellei and Griffel, I958). 4. A n u m b e r of cases showed on histopathological examination inflammatory interstitial infiltration in other parts of the body (liver, diaphragm, psoas muscles, pericardium, etc.). T h e r e exist comprehensive clinical as well as pathological studies of the disease (Saphir, 1942;
Saphir, Wile, and Reingold, I944; Tedeschi and Stevenson, 1951 ; L i n d and Hultquist, 1949; and others). T h e aetiology of t h e disease, however, is unknown. Until now the causative agent has not been established, though in some outbreaks Coxsackie group B virus was found associated v?ith the disease (in Johannesburg as well as in the Rhodesian butbreak). Radiological studies of the disease are scarce, though in clinical reviews (Williams, O'Reilly, and Williams, 1953; Rosenbaum, Nodas, and Neuhauser, 1953; Brigden, 1957; and others) the radiological appearances of the disease are reported. D u r i n g the last io years, however (as far as the present authors could ascertain), no paper on the subject has appeared in the radiological literature. T h e purpose of t h i s paper is to : - 1. Report the rac[tblogical observations in the 33 cases radiographed. 2. Define the radiological features of the disease. 3. Point out the differential diagnostic considerations which may lead to the establishment of the correct diagnosis. PRESENTATION O F T H E 33 C A S E S RADIOGRAPHED AND RADIOLOGICAL , OBSERVATIONS
Age, Sex, and M o r t a l i t y . Age-group: 6 - I Z
Age-group:
Age-group:
months.--
Sex
Total
Male Female
9 :4
Survived I I
Died 8 3
Total
13
2
Ii
Male Female
3 IO
2 3
7
Total
13
5
8
years.-Male Female
7 o
4 o
3 o
7
13-18 months,-
I9 months--3½
Total All groups.--
Male Female
19 14
4 7 4
lZ io
Total
33
II
22
Date of A d m i s s i o n . May-December, January--December,
I956 I957
9 24
Provisional Diagnosis from Admission R o o m . Acute m y o c a r d i t i s Myocarditis or pneumonia Pneumonia or myocarditis Pneumonia Respiratory foreign body Bronchitis spastica Ileus Intussusception Paralysis of diaphragm or myocarditis No more definite diagnosis on admission Total
11 2 3 4 4 2 I I i 4 33
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Signs of Right Heart Failure (enlarged liver).-All cases.
Radiological Appearance of Heart Enlargement.-Stage I
Stage l I
6
I6
Stage I11
Total 33
xx
Radiological Signs of Passive Pulmonary Congestion.Present Absent Total 29
4
33
Kerley's B Lines.DefinitelySeen Doubtful
Not Seen
Total
I5
33
15
3
Heart Pulsations.Visible Faintly Visible I
Not Seen
Not Screened
Total
7
I6
33
9
Radiological Signs of Pleural F l u i d . Right Left Bilateral None Total 7 3 I8 5 Interlobar fluid in addition to costal fluid
33 13
Radiological Signs of other PulmOnary Changes.Emphysema Pneumonia of Alveolar Type None Total z7
2
I4
Course of Disease.Diedshortly after Died after
33
First Examination
First Relapse
Died after Second Relapse
Total
20
I
I
22
Survived without Relapse
Survived after One Relapse
Total
8
3
II
Autopsy Findings.--Cases radiographed 33. Cases died 22. Autopsies performed zI. Interstitial myocarditis all cases Congestion of lungs all cases (Edema of lungs all cases Pericardiat fluid 5 Pleural fluid 6 Ascites z Congestion of liver all cases Interstitial infiltration of lungs I~ Alveolar infiltration of lungs • Subendocardial thickening and fibrosis 8 Interstitial infiltration in other organs (portal areas of liver, muscles, etc.) 7
C o m m e n t . - - T h e provisional diagnoses from the admission room prove how difficult it may be to distinguish clinically in infants and small children between acute heart failure due to myocarditis affd acute respiratory infection (pneumonias). This is discussed in this paper ui~der "Differential Diagnostic Considerations . In z cases abdominal signs were predominant, a well-known occurrence in respiratory infections. Th e X-ray examination of the abdomen showed gas-distended bowel with several fluid levels. (The barium enema revealed a normal colon.) This can be explained by the swallowing of air as part of the anoxia of the child. T h e three stages of heart enlargement, the signs of passive pulmonary congestion, and the additional pulmonary changes are discussed under " T h e 1Radiological Features of the Disease". Electrocardiographic examinations were performed in 25 cases. Sinus tachycardia was invariably present with a pulse-rate of over 15o per minute. The T waves were flat or negative in most leads and the S-T segment was below the iso-electric line. In the majority of cases the QRS complex was very low. In the children who recovered the electrocardiogram returned to normal.
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T H E R A D I O L O G I C A L F E A T U R E S OF THE DISEASE I. T h e S i z e and S h a p e o f the H e a r t . ~ General enlargement ot7 the heart is the predominant feature of the disease and it was seen in all cases. However, according to the size and shape of the heart three stages could be clearly distinguished. Stage / . - - I n which the dilatation is of slight degree, the shape of the heart being well preserved. T h e individual heart chambers are easily distinguish. able. In these cases the enlargement of the heart can be easily missed, particularly if there are no signs of pulmonary congestion (Case i, Fig. i). Stage H . - - I n which the general enlargement of the heart is very marked. T h e shape of the heart, however, is still preserved and radiological differentiation between the individual heart chambers is still possible (myopathic heart configuration--Holzmann, 1952). We did not notice any predominance in the enlargement of the individual chambers (Case 2,
Fig. 2). Stage I I L - - T h e general enlargement is of extreme degree ; the individual heart chambers are no longer distinguishable; the heart silhouette is globular in shape with a broad base. It is hardly possible to differentiate at this stage radiologically from pericardial effusion (pericarditis), all the more because in both these conditions the amplitude of pulsation is markedly diminished or the pulsations no longer visible. In addition, at autopsy examination small amounts of pericardial fluid were found in these cases of myocarditis (Case 3, Fig. 3). Change from Stage II to Stage I I I was noted in 2 cases and in another case change from Stage I to Stage I I I was seen (Case 4). This shows that given time for radiological observation gradual increase of the size of the heart can be noted. It proves that the described stages are only phases in the increasing myopathic dilatation of the heart. On the other hand, in the cases which survived, a gradual decrease of the size of the heart over a period of months was observed, with eventual return to normal (Case 4, Fig. 4). No relation between the size of the heart and the degree of passive pulmonary congestion was noted. In this series very slightly enlarged hearts (Stage I) were seen with a very marked degree of pulmonary congestion, while on t h e other hand, very marked dilatations of the heart (Stage III) with no signs or very slight signs of pulmonary congestion were observed.
:~. P a s s i v e
Pulmonary
Congestion.--Apart
from 4 cases (i with heart dilatation of Stage I, 2 with heart dilatation Stage II, and i with heart dilatation Stage III) all cases showed signs of passive pulmonary congestion on the first X-ray examination on admission. I n the majority of the cases the congestion presented itself by structural intensification spreading from the hilum into the lung fields, following the interstitial pattern into its most peripheral distributions (third zone). In addition, some degree of haziness of the lung fields was present, more marked in the perihilar regions. In most of the cases there was no marked enlargement of the hilar shadows. There could be no doubt that these appearances were caused by engorgement of the pulmonary arteries and veins due to cardiac failure. As a
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confirmatory factor, Kerley's B lines were noted in, and also just above, the costophrenic angle (more commonly on the right side), giving evidence of lymphatic engorgement (Kerley, 1951 ; Bruwer, 1956 ; Esch and Thurn, 1957). T h e presence of these B lines in acute left heart failure due to acute myocardial disease is important evidence in the evaluation of these lines. It proves that they can develop within
Fig. I.--Case I . H e a r t enlargement Stage I. into its most peripheral distribution (third zone). of the lungs. Ttxe child died within 24 hours after addition to signs of interstitial myocarditis evidence
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these children showed recessions.) It is a leading sign in acute respiratory infections (acute laryngotracheitis, acute diffuse interstitial pneumonia, etc.). In addition, the haziness of the lung fields was less marked, and the pathological interstitial pattern was shown mainly in the paramediastinal regions, leaving the peripheral zone (outer third) free. These appearances ind4aced us to think in these cases of the presence
Signs of pulmonary passive congestion following the interstitial pattern Signs of costal as well as interlobar pleural fluid. M a r k e d emphysema the X - r a y examination. T h e histopathological examination showed in of interstitial inflammation of the lungs.
Fig. 2.--Case 2. Generalized heart enlargement Stage I I (myopathic heart configuration). Signs of m a r k e d pulmonary passive congestion following the interstitial pattern into its m o s t peripheral distributions (third zone). Evidence of pleural fluid (costal and interlobar)..Marked e m p h y s e m a Of the lungs. T h e child died within 24 hours after the X - r a y examination. T h e histopathological examination showed in addition to interstitial myocarditis evidence of diffuse interstitial inflamm a t o r y infiltration of the lungs.
a very short time. In those of our cases in which the disappearance of the pulmonary congestion could be observed radiologically the B lines disappeared as quickly as the other signs of passive congestion, which is proof of their reversibility within a very short time (Case 5, Fig. 5). There were cases, however, in which the appearance of the interstitial pattern of the lungs did not permit such a definite conclusion. Many of these cases showed marked emphysema which can be explained only by expiratory impairment. (Some of
Fig. 3.--Case 3. Generalized heart enlargement Stage I I I . Typical appearance of passive p u l m o n a r y congestion, m o s t m a r k e d in the perihilar regions, T h e child died a few hours after the X - r a y examination.
of diffuse interstitial pneumonia (pneumonitis). This form of pneumonia is commonly seen in Israel, primary or secondary, e.g., in whooping-cough or measles. During the period in which the cases of myocarditis were seen several cases Of diffuse interstitial pneumonia made their appearance in the X-ray Department. In these a very important feature was the emphysema of the lungs with the concomitant small heart. In all of our cases of primary interstitial myocarditis, however, the heart was clearly enlarged even in the presence of marked emphysema; this led us to assume that in addition to myocarditis, diffuse interstitial pneumonia was present. T h e following case may serve as an illustration (Fig. 6).
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A
B
C
D
E
Fig. 4.--Case 4.
A, Oct. 9, I956. Generalized heart enlargement (Stage II). M a r k e d pulmonary passive congestion following the, interstitial pattern into the peripheral (third) zone. Pleural costal fluid, left and interlobar, right. B, Oct. I2. Increase in size of heart (Stage I I I ) . Pulmonary passive congestion unchanged. :Pleural fluid now bilateral. C, Oct. I5. M a r k e d decrease in s i z e of heart. L u n g fields normal (congestion of lungs no more shown). D, Nov. 23. Five weeks later. Relapse: again generalized heart enlargement shown w i t h marked pulmonary passive congestion. T h e child recovered after radical digitalis and antibiotic treatment. E, Nov. 7, I957. O n e year later. Return to normal.
Fig. 5.--Case 5. Kerley's B lines clearly shown in a case of heart enlargement of Stage I I w i t h m a r k e d pulmonary passive congestion. Note bandlike shadow at lateral chest wall (pleural fluid), the B lines reaching its medial border.
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Case 6 . - - O n first examination (Sept. 13, 1956, Fig. 6 A) the heart was slightly enlarged, marked e m p h y s e m a was sh6wn, and the pathological interstitial pattern was seen invading the paramediastinal regions, leaving the peripheral zone (third zone) free, an appearance commonly seen in diffuse interstitial pneumonia. T h r e e days later (Sept. i6, Fig. 6 B) the emphysema and the above-mention pedathologicalinterstitial p a t t e m w e r e no more shown, the dilatation of the heart was slightly more marked, and slight perihilar
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T e d e s c h i a n d S t e v e n s o n (1951) s h o w 2 cases o f primary interstitial myocarditis associated with interstitial p n e u m o n i a . T h e s e a u t h o r s w r i t e : " A p n e u m o n i c p r o c e s s w a s s u s p e c t e d in b o t h o n X - r a y e x a m i n a t i o n , c o n f i r m e d at a u t o p s y a n d classified as interstitial in t y p e . " R o s e n b a u m a n d o t h e r s (1953) mention 4 patients "in whom the differentiation betweer~primary myocardial disease and myocarditis
A
B
c
D
Fig. 6.--Case 6. A, Sept. x3, I956. Slight dilatation of the heart silhouette. Marked structural intensification involving
the paramediastinal regions, leaving the peripheral (third) zone free. Marked emphysema. B, Sept. i6, The emphysema and the pathological interstitial pattern no longer shown. Slight increase in the size of the heart silhouette. Slight perihilar cedema. C, Sept. I9. Perihilar congestion more marked. D, June iz, I957. Nine months later. Return to normal. (The child recovered after radical antibiotic and digitalis treatment.) oedema was noted. T h r e e days later (Sept. I9, Fig. 6 C) a slight increase in the size of the heart was noticeable, the perihilar eedema being still present. T e n days later (Sept. 26) diffuse pulmonary ~edema was seen. T h e child received radical digitalis and antibiotic treatment and recovered, the heart r e t u r n i n g gradually to normal within nine m o n t h s (Fig. 6 D). W e believe that in this case the predominant radiological features on first examination were those of diffuse interstitial pneumonia, although a myocarditis was already present, the heart silhouette being slightly enlarged.
s e c o n d a r y to p n e u m o n i t i s was p r a c t i c a l l y i m p o s s i b l e : t h e s e 4 p a t i e n t s h a d p h y s i c a l s i g n s o f rfiles a n d h a r s h b r e a t h s o u n d s w i t h c h e s t films e q u a l l y s u g g e s t i v e o f i n f l a m m a t i o n or c o n g e s t i o n . " T h e cases in w h i c h t h e h i s t o p a t h o l o g i c a l e x a m i n a t i o n (Gellei a n d Griffel, 1958) s h o w e d i n t e r s t i t i a l i n f l a m m a t o r y i n f i l t r a t i o n o f t h e l u n g s are p r o o f t h a t t h e c o m b i n a t i o n o f p r i m a r y interstitial myocarditis with interstitial pneumonia ( p n e u m o n i t i s ) m u s t b e a relatively f r e q u e n t o c c u r r e n c e . T h i s w o u l d s u p p o r t t h e v i e w o f a viral o r i g i n
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of primary interstitial myocarditis. There were cases in which radiological evidence of perihilar cedema was present; only in one case was generalized pulmonary cedema seen. As mentioned before, 4 cases showed no radiological signs of passive pulmonary congestion and yet the children died a few hours after the X-ray examination as did those with a very marked pulmonary congestion (Case 7, Fig. 7).
Fig. 7.--Case 7. Generalized heart enlargement of Stage I I (myopathie configuration of the heart). N o radiologicaI signs of passive pulmonary congestion. M a r k e d e m p h y s e m a of the lungs. Bronchopneumonic foci are shown in right upper lobe as well as in apex of right lower lobe. T h e child died a few hours after the X - r a y examination. O n histopathological examination, evidence of interstitial myocarditis, m a r k e d congestion and cedema of lungs, bronchopneumonie foei, and slight interstitial inflammatory infiltration of the lungs.
This suggests that neither from the size or shape of the heart nor from the degree of pulmonary congestion can prognostic deductions be drawn. In the children who did not die within hours after the X-ray examination and in whom further radiological observation was thus possible, the signs of pulmonary congestion could be seen to disappear within a few days. In some of the children one to two relapses could be observed clinically as well as radiologically, the tachycardia being the first sign of the relapse, followed by the reappearance of all signs of pulmonary congestion (Case 4, Fig. 4; Case 8, Fig. 8). 3. P l e u r a l F l u i d . - - I n all but 5 cases pleural fluid was seen as a bandlike shadow along the lateral chest wall, sometimes unilateral, sometimes bilateral. This sign is well known (Holzmann, 1952; Schiifer, 1955) and can be explained by transudation into the pleural cavity. In 13 cases, in addition, small amounts of interlobar fluid were noted. There exists a discrepancy between the radiological and the autopsy findings. At autopsy in 6 cases only pleural fluid was found. There is, however, no other radiological explanation for these bandlike shadows along the lateral chest wall seen in all except five of the cases. 4. P u l s a t i o n s o f the H e a r t . - - O f the 33 cases 17 were screened in addition to films being taken. Of these, i6 showed very weakened or indistinguishable pulsations. It must, however, be borne in mind that to judge the amplitude of the pulsation may be very difficult because of the ever present tachycardia
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(I50--2OO heart-beats per minute in the majority of cases). No relation could be established between the size of the heart and the amplitude of pulsations. Though the dilatation bf the heart may be of small degree (Stage I or II) and the heart-beat may be scarcely visible, there may on the other hand be very marked dilatation of the heart (Stage III) with pulsa. tion still distinguishable. An important sign of the beginning of recovery (under digitalis treatment) is the reappearance of visible pulsation, which becomes clearly distinguish. able with the diminishing pulse-rate. On the other hand, as has been mentioned, the recurrence of tachycardia was seen as the first sign of a relapse. DIFFERENTIAL DIAGNOSTIC CONSIDERATIONS 1. T h e most important task of the radiologist, according to our experience during the epidemic, is the differentiation between acute pulmonary inflammatory disease and primary interstitial myocarditis. This becomes apparent on reading the following sentences in the clinical study of Williams and others (1953): " T h e pattern of cardiac failure in young infants can be a confusing one unless encountered previously. Disturbed, rapid breathing, cyanosis, cold extremities, poor capillary circulation and tachycardia occur in both cardiac failure and severe respiratory tract infection, especially pneumonia. Failure to demonstrate cardiac enlargement is the most important reason for mistaking acute heart failure for pneumonia." T h e differentiation will be easy if definite radiological evidence of lobar or lobular pneumonia is present, relieving the anxiety of the physician as well as of the radiologist for those children who are brought into the hospital in this severe condition. It has to be borne in mind, however, that these pneumonias may also be associated with myocarditis caused by the same agent, which makes careful radiological examination of the heart in these cases essential (see also under 3). T h e task of the radiologist becomes very difficult and sometimes impossible in the differentiation between primary interstitial myocarditis and diffuse interstitial pneumonia (pneumonitis). As has been mentioned before, cases of the latter kind are rather common in Israel and several of them were seen in the X-ray Department during the epidemic. In such cases, the radiologist and the physician have to decide quickly because energetic cardiac treatment introduced immediately may save the life of a child suffering from myocarditis. The differential diagnostic features are as follows. In diffuse interstitial pneumonia one of the leading. signs is the marked emphysema due to expiratory impairment. T h e heart is small in most of the cases. T h e pathological interstitial pattern is usually limited to the paramediastinal region (along its whole length), leaving the peripheral (third) zone free. The latter zone is usually involved in passive pulmonary congestion due to heart failure in myocarditis. We have reviewed our cases of primary and secondary diffuse interstitial pneumonia and in none of them were Kerley's B lines seen. We consider the presence of these lines to be an important differential diagnostic sign, giving evidence of passive pulmonary congestion. T h e almost invariable
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presence of costal or interlobar pleural fluid in heart failure due to myocarditis may be of help in the diagnosis. In our experience it is a very rare occurrence in interstitial pneumonias. In acute bronchiolitis in which the clinical signs may be as severe as in myocarditis, the heart is normal and the pathological pattern of the lungs differs markedly from passive congestion, showing a fine granular miliary pattern. In acute laryngo-tracheo-bronchitis marked emphysema due to expiratory impairment is present, together with inspiratory distress, seen on fluoroscopy as inspiratory widening of the heart shadow (Munk
congestion caused a pathological interstitial pattern reaching into its most peripheral distributions (third zone). Kerley's B lines were usually present. T h e only definite sign of inflammatory interstitial (bronchial) involvement of the lungs was the emphysema
A
B
C D A, Jan. 25, I 9 5 7 . H e a r t enlargement Stage I I . M a r k e d signs o f pulmonary passive congestion spreading into the m o s t peripheral part of the lungs (third zone). Evidence of costal and interlobar fluid. M a r k e d e m p h y s e m a of the lungs. B, T a k e n f r o m film of Jan. 25, showing the peripheral zone. C, Feb. 7. Decrease in size of heart. T h e pulmonary congestion as well as the e m p h y s e m a no longer shown D, .Feb I8. Eleven days later. Relapse: M a r k e d pulmonary congestion. T h e child died a few hours after this .N-ray examination. O n histopathologicaI examination, interstitial myocarditis, congestion of lungs, pleural fluid, bronchopnanmonie loci, and h m m o r r h a g e s . Sub-endocardial fibrosis in the subaortic region. Pericardial fluid.
Fig. 8.--Case 8.
and Lederer, I954). T h e heart is usually of normal size. However, the differential diagnosis becomes very complicated in cases of combined diffuse interstitial pneumonia and myocarditis. As has been shown, I I out of 27 patients with myocarditis who died in 1957 presented histopathological evidence of interstitial inflammation of the lungs, the interalveolar and interlobular septa as well as the peribronchial structures being mainly involved. We searched for radiological signs which would prove the presence of both conditions. T h e passive pulmonary I5
due to expiratory impairment, but when this was combined with an enlarged heart it suggested that, in addition to interstitial pneumonia, myocarditis was present. There may be, however, at the first examination, a barely noticeable enlargement of the heart and the pathological interstitial pattern suggestive of interstitial pneumonia (see Case 6), and only at the second examination a few days later does the heart enlargement become apparent. This shows that in some cases a definite radiological conclusion as to the presence of both conditions may be impossible on the first examination.
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2. T h e radiological differentiation between primary interstitial myocarditis and other forms of primary myocardial disease is ~very limited. This applies particularly to sub-endocardial fibro-elastosis which is usually seen in the X-ray department at the stage of cardiac failure, presenting all the clinical as well as radiological signs shown in primary interstitial myocarditis. As has been mentioned before, a large percentage of cases in our series of myocarditis showed histopathological evidence of sub-endocardial fibrosis, supporting the view of Rosenbaum and co-workers (i953) that "sub-endocardial sclerosis may not be primary in itself but rather a response of the tissues to some basic stimulus such as anoxia". This view of these authors is based on the fact that in primary interstitial myocarditis as well as in aberrant left coronary arteries and in medial necrosis of the coronary arteries endocardial thickening is a frequent finding. We have no experience with the latter two entities. According to Rosenbaum and co-workers in both these conditions a differential diagnostic feature is, in addition to clinical considerations, the absence of congestive failure. T h e same applies, according to these authors, to glycogen storage disease of the heart. 3. It is impossible to differentiate on radiological grounds between primary interstitial myocarditis and secondary myocarditis because the radiological features are the same. Saphir and others (I944), in 97 cases of myocarditis in children, found i case of postdiphtheritic inflammation of the myocardium, 4 patients with meningitis, 7 with poliomyelitis, 12 with bronchopneumonia, 3 with lobar pneumonia, 3 with nephritis, 5 with bacterial endocarditis, 7 with 'rheumatic type' myocarditis, 14 true cases of rheumatic myocarditis, 3 of isolated myocarditis, and 4 of myocarditis associated with tuberculosis. Apart from the pneumonias, as has been discussed before, the differentiation between these individual forms of secondary myocarditis will remain the task of the physician. T h e responsibility of the radiologist will be to confirm the clinically suspected myocarditis in the diseases mentioned. 4- Generalized heart enlargement with pulmonary congestion in decompensated rheumatic carditis may present the same radiological appearance 'as cardiac failure due to myocarditis. Here, too, the heart may be uniformly enlarged and the differentiation between the individual chambers may be impossible so that no signs pointing to a particular valvular involvement may be present. It still occurs, though rarely, that cases of rheumatic heart disease make their first appearance in the hospital and in the X-ray department at this advanced stage of the disease. It is well known, however, that rheumatic disease of the heart does not appear during the first year of life--in which so many of our cases of primary interstitial myocarditis occurred--and usually does not develop ~efore the fourth year of life. 5. Decompensated congenital cardiac disease may present a very difficult differential diagnostic problem, particularly in the second half of the first year of life, in which so many cases of primary interstitial myocarditis occur, and when the appearance of the heart does not offer any differentiating signs. T h e globular heart present in these conditions in infancy and early childhood offers few possibilities
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to evaluate the size of the pulmonary trunk which is so valuable a sign in older children and in adults. T h e radiological appearafice of the hilar and mid-zone branches of the pulmonary arteries may help in the differential diagnosis. T h e differentiation between passive pulmonary congestion due to mitral heart disease or left cardiac failure, and active arterial overflow due to an extra- or intracardial left-to-right shunt, is usually possible because of the differing appearance of the hilar and mid-zone branches of the pulmonary arteries. Well-defined, markedly dilated hilar and mid-zone arterial branches will point in favour of a left'to-right shunt. Pulsations of these arteries in infants and small children are, how. ever, difficult to observe. In the majority of our cases of myocarditis no marked enlargement of the hilar arteries (hilar shadows) was noted, the reason being that the heart failure develops suddenly and the engorgement of the bigger branches of the pulmonary arteries does not reach any marked degree. 6. As has been mentioned before, the radiological differentiation between primary interstitial myocarditis (Stage I I I of heart enlargement) and pericardial effusion (pericarditis) may be impossible from the appearance of the heart. In addition, decrease or disappearance of visible cardiac pulsations is noted in both. However, pulmonary passive congestion (left heart failure) is in our experience rarely seen in pericarditis, even with very extensive enlargement of the heart silhouette due to large amounts of pericardial fluid.
SUMMARY Th e radiological observations in 33 cases of primary interstitial myocarditis in the age-group 6 months to 3½ years are reported. T h e radiological features of the disease are presented. According to the size and shape of the heart, three stages of myopathic heart configuration are shown, presenting phases of the increasing myogenic dilatation of the heart. In cases that permitted further observation, gradual decrease of the size of the heart with eventual return to normal could be seen. T h e radiological appearances of passive pulmonary congestion, which were present in all but 4 cases, are discussed. Cases are presented with the typical appearances of arterial venous and lymphatic engorgement extending into the most peripheral parts of the lung fields (third zone) together with Kerley's B lines. In addition, cases are reported with a pathological interstitial pattern suggestive of diffuse interstitial pneumonia, these cases showing marked emphysema. T h e deduction is drawn that the combination of primary interstitial myocarditis with diffuse interstitial pneumonia must be a relatively frequent occurrence. This is supported by the fact that I I out of 27 patients who died in i957 showed on histopathological examination evidence of interstitial inflammatory infiltration of the lungs, in addition to interstitial myocarditis. Radiological evidence of pleural fluid was seen in 28 out of the 33 cases. Diminished or invisible cardiac pulsations may be of diagnostic aid. T h e radiological differential diagnostic considerations are discussed. T h e most important task of the radiologist is considered to be the differentiation between acute inflammatory pulmonary disease and
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myocarditis, the presenting severe clinical signs in both these conditions making a clinical differentiation sometimes very difficult. T h e differential diagnostic features between heart failure due to myocarditis and diffuse interstitial pneumonia are described, marked emphysema with a small heart and absence of Kerley's B lines pointing in favour of the latter. In addition the pathological interstitial pattern in diffuse interstitial pneumonia is usually limited to the paramediastinal regions (leaving the outer third free). T h e fine granular miliary pattern in acute bronchiolitis is thought to permit differentiation of this disease. T h e radiological signs of ~he combination of primary interstitial myocarditis with diffuse interstitial pneumonia are discussed, the most important feature being a marked emphysema and at the same time an enlarged heart. T h e differentiation from other forms of primary myocardial disease is mentioned; sub-endocardial fibro-elastosis offers no differentiating radiological signs. T h e radiological appearance of secondary myocarditis due t o diphtheria, poliomyelitis, meningitis, nephritis, bacterial endocarditis, etc., presents no radiological differential diagnostic features. T h e differential diagnostic considerations between myocarditis and decompensated rheumatic carditis as well as decompensated congenital cardiac disease are mentioned. An important differential diagnostic sign between primary interstitial myocarditis and pericardial effusion (pericarditis) is believed to be the rare or very late occurrence of left heart failure (passive pulmonary congestion) in the latter.
Acknowledgements.--Dr. J. Munk wishes to express his sincere thanks to Dr. Peter Kerley for the valuable knowledge gained at the X-ray Departments of the Westminster Hospital and of the National Heart Hospital in London. Much help was thus obtained in the writing of this paper. T h e authors wish to thank Dr. W. Falk and Dr. E. Freundlich of the Department of Pmdiatrics B, Dr. J. Bar-Hay and Dr. M. Berkowitz from the Department of P~ediatrics A, Rambam Government Hospital, Haifa, for their help and co-operation; Dr. B. Gellei and Dr. S. Griffel from the Department of Pathology, Rambam Government Hospital, Haifa, for their aid and valuable advice ; Dr. B. Ostrowsky, Dr. S. T. Winter, Dr. Z. Sehwarz, and Dr. W. Sh. Moses from the Rothschild Hospital, Haifa, for their kind permission to include their cases in this paper.
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Thanks are due to the medical staff of the X-ray Department of the Rambam Government Hospital, Haifa, Dr. A. Jungmann, Dr. L. Rolan, Dr. E. Hahn, and Dr. P. Boldo for their continued interest which made the publication of the paper possible. REFERENCES BRIGDEN,W. (I957), Lancet, 2, 1179, 1243. BRUW~R, A. J. (1956), Amer. J. Roentgenol., 76, 4CAFFEY, J. (I956), Pediatric X-ray Diagnosis. Chicago: The Yearbook Publishers. CHOREMIS, C., CASSIMOS, CH., 'NIKOYANNOPOULOS,J., MAVROU, K., and HAKA, C. (I956), Ann. Pediat., 187, 444. "\ EBNOTHER, C. L., and ABRAMS, H. L. (I957), "Amer. J. Roentgenol., 77, 2. EscH, D., and THURN, P. (I957), Fortschr. R6ntgenstr., 87, 7FIEDLER, A. (19oo), Zbl. inn. Med., 21, 212. Fr~UNDLICH, E., BERKOWlTZ, M., ELKON, A., and WILDER,A: (z958), Amer.J. Dis. Child., to be published. GELLEI,. B., and GRIEFEL, S. (1958), personal communication. HOLZMANN, M. (I952), Lehrbuch der R6ntgendiagnostik (ed. H. R. SCHINZ, W. E. BAENSCH, E. FRIEDL, and E. UEHEINGER), 5th ed., vol. 3, P. 2828. Stuttgart: G. Thieme. JAVETT, S. N., HEYMANN,$!/S.,MUNDEL, B., PEPLER, W. J., LURIE, H. J., GEAR, J., MEASROCK,V., and KIRSCH, Z. (I956), J. Pediat., 48, I. KERLEY, P. (I95I), Textbook of X - r a y Diagnosis (ed: S. C. SHANKSand P. KERLEY), 2nd ed., vol. 2, p. 405 . Philadelphia: Saunders. LIND, J., and HULTQUIST,G. T. (i949) , Amer. Heart ft., 38, z23. MONTGOMERY, J., GEAR, J., PRINSLOO, F. R., KAHN, M., and KIRSCH, Z. (I955), S. Afr. reed. J., 29, 608. MUNK, J., and LEDEmm, K. T. (I954), Brit. J. Radiol., 27, 294. ROSENBAUM, H. D., NADAS, A. S., and NEUHAUSER, E. B. D. (I953), Amer. J. Dis. Child., 86, 28. SAPHIR, O. (I942), Amer. HeartJ., 24, 167. - - - - WILE, S. A., and REINGOLD, I. M. (I944) , Amer. J. Dis. Child., 67, 294. SCHXEER, K. H. (I955), PfidiatriScher RSntgenatlas. Stuttgart: G. Thieme. STOEBER, E. (I952), Z. Kinderheilk., 71, 319, 592. TEDESCHI, C. G., and STEVENSON, T. D. (I95I), New EngL J. Med., 244, 352. VAN Cm~VELD, S., and JAGER, H. (I956), Ann. Pediat., 187, zoo. WILLIAMS, H., O'REILLY, R. N., and WILLIAMS,A. (I953) , Arch. Dis. Childh., 28, 14o. ZDANSKY, E. (I957), R6"ntgendiagnostik, Ergebnisse 19521956 (ed. H. R. SCHINZ, R. GLAUNER, and E. UEHLINGER), p. IO4. Stuttgart: G. Thieme. ZUPPINGER, H. (i9oi), Wien. klin. Wschr., 14, 799.
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MYOCARDITIS
Radiological Observations on 33 Cases of Primary Interstitial Myocarditis during an Outbreak in the Haifa Area J. M U N K , M.D., ANn K. T. LEDERER, M.D.
X-ray Department, Rambam Government 1-32fs}ital, Haifa, lsrael OUT of 61 cases of primary interstitial myocarditis (idiopathic myocarditis) in children in the age-group between 6 months and 3½ years, which occurred in the Haifa area between May, 1956, and D e c e m b e r , 1957, 33 were radiographed (z8 in this hospital and 5 in the Rothschild Hospital, Haifa). Fifty of the children died and in all these, except one, the diagnosis was confirmed by p o s t - m o r t e m examination ; I I children survived. T h e 28 children who died without previous X - r a y examination arrived at the hospital either in extremis or already deceased. F r o m the clinical as well as from the epidemiological point of view the occurrence of the cases showed the characteristics of an epidemic outbreak and was described as such (Freundlieh, Berkowitz, Elkon, and Wilder, 1958). T h e y report on 57 cases. I n our paper 4 additional cases are included. T h e s e 4 children survived. T h e y presented radiological features which we considered typical of the disease. Primary interstitial myoearditis was first described by Fiedler (19oo) in an adult and by Z u p p i n g e r (19Ol) in a child. Since then reports On small groups of cases have appeared in the literature from various parts of the world. T h e greatest n u m b e r of cases described (14o) occurred in M u n i c h during the years 1937-44 (Stoeber, 1952). In recent years, however, several outbreaks of epidemic character were reported : one comprising IO cases was reported from a maternity h o m e in Johannesburg (Javett, H e y m a n n , M u n d e l , Pepler, Lurie, Gear, Measrock, and Kirsch, 1956), a further outbreak of 9 cases in a maternity h o m e in Southern Rhodesia (Montgomery, Gear, Prinsloo, Kahn, and Kirsch, I955) , 4 cases in A m s t e r d a m (van Creveld and Jager, I956), and 8 cases in Athens reported by Choremis, Cassimos, Nikoyannopoulos, Mavrou, and Haka (1956). T h e main features of this outbreak in the Haifa area were t h a t : - I. Within a period of 20 months 6I cases occurred in the relatively small Haifa district, while f r o m other parts of the country no increase above the usual n u m b e r of cases ( i - 2 a year in each of the big hospitals) was reported, which points in favour of the epidemic character of the occurrence. 2. Eleven out of 27 patients who died in 1957 showed histopathological evidence of diffuse interstitial pneumonia in addition to typical pathological signs of primary interstitial myocarditis, 3. Eight out of the 27 patients who died in 1957 presented on histopathological examination in addition to signs of interstitial myocarditis areas of subendocardial fibrosis (Gellei and Griffel, I958). 4. A n u m b e r of cases showed on histopathological examination inflammatory interstitial infiltration in other parts of the body (liver, diaphragm, psoas muscles, pericardium, etc.). T h e r e exist comprehensive clinical as well as pathological studies of the disease (Saphir, 1942;
Saphir, Wile, and Reingold, I944; Tedeschi and Stevenson, 1951 ; L i n d and Hultquist, 1949; and others). T h e aetiology of t h e disease, however, is unknown. Until now the causative agent has not been established, though in some outbreaks Coxsackie group B virus was found associated v?ith the disease (in Johannesburg as well as in the Rhodesian butbreak). Radiological studies of the disease are scarce, though in clinical reviews (Williams, O'Reilly, and Williams, 1953; Rosenbaum, Nodas, and Neuhauser, 1953; Brigden, 1957; and others) the radiological appearances of the disease are reported. D u r i n g the last io years, however (as far as the present authors could ascertain), no paper on the subject has appeared in the radiological literature. T h e purpose of t h i s paper is to : - 1. Report the rac[tblogical observations in the 33 cases radiographed. 2. Define the radiological features of the disease. 3. Point out the differential diagnostic considerations which may lead to the establishment of the correct diagnosis. PRESENTATION O F T H E 33 C A S E S RADIOGRAPHED AND RADIOLOGICAL , OBSERVATIONS
Age, Sex, and M o r t a l i t y . Age-group: 6 - I Z
Age-group:
Age-group:
months.--
Sex
Total
Male Female
9 :4
Survived I I
Died 8 3
Total
13
2
Ii
Male Female
3 IO
2 3
7
Total
13
5
8
years.-Male Female
7 o
4 o
3 o
7
13-18 months,-
I9 months--3½
Total All groups.--
Male Female
19 14
4 7 4
lZ io
Total
33
II
22
Date of A d m i s s i o n . May-December, January--December,
I956 I957
9 24
Provisional Diagnosis from Admission R o o m . Acute m y o c a r d i t i s Myocarditis or pneumonia Pneumonia or myocarditis Pneumonia Respiratory foreign body Bronchitis spastica Ileus Intussusception Paralysis of diaphragm or myocarditis No more definite diagnosis on admission Total
11 2 3 4 4 2 I I i 4 33
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Signs of Right Heart Failure (enlarged liver).-All cases.
Radiological Appearance of Heart Enlargement.-Stage I
Stage l I
6
I6
Stage I11
Total 33
xx
Radiological Signs of Passive Pulmonary Congestion.Present Absent Total 29
4
33
Kerley's B Lines.DefinitelySeen Doubtful
Not Seen
Total
I5
33
15
3
Heart Pulsations.Visible Faintly Visible I
Not Seen
Not Screened
Total
7
I6
33
9
Radiological Signs of Pleural F l u i d . Right Left Bilateral None Total 7 3 I8 5 Interlobar fluid in addition to costal fluid
33 13
Radiological Signs of other PulmOnary Changes.Emphysema Pneumonia of Alveolar Type None Total z7
2
I4
Course of Disease.Diedshortly after Died after
33
First Examination
First Relapse
Died after Second Relapse
Total
20
I
I
22
Survived without Relapse
Survived after One Relapse
Total
8
3
II
Autopsy Findings.--Cases radiographed 33. Cases died 22. Autopsies performed zI. Interstitial myocarditis all cases Congestion of lungs all cases (Edema of lungs all cases Pericardiat fluid 5 Pleural fluid 6 Ascites z Congestion of liver all cases Interstitial infiltration of lungs I~ Alveolar infiltration of lungs • Subendocardial thickening and fibrosis 8 Interstitial infiltration in other organs (portal areas of liver, muscles, etc.) 7
C o m m e n t . - - T h e provisional diagnoses from the admission room prove how difficult it may be to distinguish clinically in infants and small children between acute heart failure due to myocarditis affd acute respiratory infection (pneumonias). This is discussed in this paper ui~der "Differential Diagnostic Considerations . In z cases abdominal signs were predominant, a well-known occurrence in respiratory infections. Th e X-ray examination of the abdomen showed gas-distended bowel with several fluid levels. (The barium enema revealed a normal colon.) This can be explained by the swallowing of air as part of the anoxia of the child. T h e three stages of heart enlargement, the signs of passive pulmonary congestion, and the additional pulmonary changes are discussed under " T h e 1Radiological Features of the Disease". Electrocardiographic examinations were performed in 25 cases. Sinus tachycardia was invariably present with a pulse-rate of over 15o per minute. The T waves were flat or negative in most leads and the S-T segment was below the iso-electric line. In the majority of cases the QRS complex was very low. In the children who recovered the electrocardiogram returned to normal.
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T H E R A D I O L O G I C A L F E A T U R E S OF THE DISEASE I. T h e S i z e and S h a p e o f the H e a r t . ~ General enlargement ot7 the heart is the predominant feature of the disease and it was seen in all cases. However, according to the size and shape of the heart three stages could be clearly distinguished. Stage / . - - I n which the dilatation is of slight degree, the shape of the heart being well preserved. T h e individual heart chambers are easily distinguish. able. In these cases the enlargement of the heart can be easily missed, particularly if there are no signs of pulmonary congestion (Case i, Fig. i). Stage H . - - I n which the general enlargement of the heart is very marked. T h e shape of the heart, however, is still preserved and radiological differentiation between the individual heart chambers is still possible (myopathic heart configuration--Holzmann, 1952). We did not notice any predominance in the enlargement of the individual chambers (Case 2,
Fig. 2). Stage I I L - - T h e general enlargement is of extreme degree ; the individual heart chambers are no longer distinguishable; the heart silhouette is globular in shape with a broad base. It is hardly possible to differentiate at this stage radiologically from pericardial effusion (pericarditis), all the more because in both these conditions the amplitude of pulsation is markedly diminished or the pulsations no longer visible. In addition, at autopsy examination small amounts of pericardial fluid were found in these cases of myocarditis (Case 3, Fig. 3). Change from Stage II to Stage I I I was noted in 2 cases and in another case change from Stage I to Stage I I I was seen (Case 4). This shows that given time for radiological observation gradual increase of the size of the heart can be noted. It proves that the described stages are only phases in the increasing myopathic dilatation of the heart. On the other hand, in the cases which survived, a gradual decrease of the size of the heart over a period of months was observed, with eventual return to normal (Case 4, Fig. 4). No relation between the size of the heart and the degree of passive pulmonary congestion was noted. In this series very slightly enlarged hearts (Stage I) were seen with a very marked degree of pulmonary congestion, while on t h e other hand, very marked dilatations of the heart (Stage III) with no signs or very slight signs of pulmonary congestion were observed.
:~. P a s s i v e
Pulmonary
Congestion.--Apart
from 4 cases (i with heart dilatation of Stage I, 2 with heart dilatation Stage II, and i with heart dilatation Stage III) all cases showed signs of passive pulmonary congestion on the first X-ray examination on admission. I n the majority of the cases the congestion presented itself by structural intensification spreading from the hilum into the lung fields, following the interstitial pattern into its most peripheral distributions (third zone). In addition, some degree of haziness of the lung fields was present, more marked in the perihilar regions. In most of the cases there was no marked enlargement of the hilar shadows. There could be no doubt that these appearances were caused by engorgement of the pulmonary arteries and veins due to cardiac failure. As a
PRIMARY
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confirmatory factor, Kerley's B lines were noted in, and also just above, the costophrenic angle (more commonly on the right side), giving evidence of lymphatic engorgement (Kerley, 1951 ; Bruwer, 1956 ; Esch and Thurn, 1957). T h e presence of these B lines in acute left heart failure due to acute myocardial disease is important evidence in the evaluation of these lines. It proves that they can develop within
Fig. I.--Case I . H e a r t enlargement Stage I. into its most peripheral distribution (third zone). of the lungs. Ttxe child died within 24 hours after addition to signs of interstitial myocarditis evidence
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these children showed recessions.) It is a leading sign in acute respiratory infections (acute laryngotracheitis, acute diffuse interstitial pneumonia, etc.). In addition, the haziness of the lung fields was less marked, and the pathological interstitial pattern was shown mainly in the paramediastinal regions, leaving the peripheral zone (outer third) free. These appearances ind4aced us to think in these cases of the presence
Signs of pulmonary passive congestion following the interstitial pattern Signs of costal as well as interlobar pleural fluid. M a r k e d emphysema the X - r a y examination. T h e histopathological examination showed in of interstitial inflammation of the lungs.
Fig. 2.--Case 2. Generalized heart enlargement Stage I I (myopathic heart configuration). Signs of m a r k e d pulmonary passive congestion following the interstitial pattern into its m o s t peripheral distributions (third zone). Evidence of pleural fluid (costal and interlobar)..Marked e m p h y s e m a Of the lungs. T h e child died within 24 hours after the X - r a y examination. T h e histopathological examination showed in addition to interstitial myocarditis evidence of diffuse interstitial inflamm a t o r y infiltration of the lungs.
a very short time. In those of our cases in which the disappearance of the pulmonary congestion could be observed radiologically the B lines disappeared as quickly as the other signs of passive congestion, which is proof of their reversibility within a very short time (Case 5, Fig. 5). There were cases, however, in which the appearance of the interstitial pattern of the lungs did not permit such a definite conclusion. Many of these cases showed marked emphysema which can be explained only by expiratory impairment. (Some of
Fig. 3.--Case 3. Generalized heart enlargement Stage I I I . Typical appearance of passive p u l m o n a r y congestion, m o s t m a r k e d in the perihilar regions, T h e child died a few hours after the X - r a y examination.
of diffuse interstitial pneumonia (pneumonitis). This form of pneumonia is commonly seen in Israel, primary or secondary, e.g., in whooping-cough or measles. During the period in which the cases of myocarditis were seen several cases Of diffuse interstitial pneumonia made their appearance in the X-ray Department. In these a very important feature was the emphysema of the lungs with the concomitant small heart. In all of our cases of primary interstitial myocarditis, however, the heart was clearly enlarged even in the presence of marked emphysema; this led us to assume that in addition to myocarditis, diffuse interstitial pneumonia was present. T h e following case may serve as an illustration (Fig. 6).
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A
B
C
D
E
Fig. 4.--Case 4.
A, Oct. 9, I956. Generalized heart enlargement (Stage II). M a r k e d pulmonary passive congestion following the, interstitial pattern into the peripheral (third) zone. Pleural costal fluid, left and interlobar, right. B, Oct. I2. Increase in size of heart (Stage I I I ) . Pulmonary passive congestion unchanged. :Pleural fluid now bilateral. C, Oct. I5. M a r k e d decrease in s i z e of heart. L u n g fields normal (congestion of lungs no more shown). D, Nov. 23. Five weeks later. Relapse: again generalized heart enlargement shown w i t h marked pulmonary passive congestion. T h e child recovered after radical digitalis and antibiotic treatment. E, Nov. 7, I957. O n e year later. Return to normal.
Fig. 5.--Case 5. Kerley's B lines clearly shown in a case of heart enlargement of Stage I I w i t h m a r k e d pulmonary passive congestion. Note bandlike shadow at lateral chest wall (pleural fluid), the B lines reaching its medial border.
PRIMARY
INTERSTITIAL
Case 6 . - - O n first examination (Sept. 13, 1956, Fig. 6 A) the heart was slightly enlarged, marked e m p h y s e m a was sh6wn, and the pathological interstitial pattern was seen invading the paramediastinal regions, leaving the peripheral zone (third zone) free, an appearance commonly seen in diffuse interstitial pneumonia. T h r e e days later (Sept. i6, Fig. 6 B) the emphysema and the above-mention pedathologicalinterstitial p a t t e m w e r e no more shown, the dilatation of the heart was slightly more marked, and slight perihilar
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199
T e d e s c h i a n d S t e v e n s o n (1951) s h o w 2 cases o f primary interstitial myocarditis associated with interstitial p n e u m o n i a . T h e s e a u t h o r s w r i t e : " A p n e u m o n i c p r o c e s s w a s s u s p e c t e d in b o t h o n X - r a y e x a m i n a t i o n , c o n f i r m e d at a u t o p s y a n d classified as interstitial in t y p e . " R o s e n b a u m a n d o t h e r s (1953) mention 4 patients "in whom the differentiation betweer~primary myocardial disease and myocarditis
A
B
c
D
Fig. 6.--Case 6. A, Sept. x3, I956. Slight dilatation of the heart silhouette. Marked structural intensification involving
the paramediastinal regions, leaving the peripheral (third) zone free. Marked emphysema. B, Sept. i6, The emphysema and the pathological interstitial pattern no longer shown. Slight increase in the size of the heart silhouette. Slight perihilar cedema. C, Sept. I9. Perihilar congestion more marked. D, June iz, I957. Nine months later. Return to normal. (The child recovered after radical antibiotic and digitalis treatment.) oedema was noted. T h r e e days later (Sept. I9, Fig. 6 C) a slight increase in the size of the heart was noticeable, the perihilar eedema being still present. T e n days later (Sept. 26) diffuse pulmonary ~edema was seen. T h e child received radical digitalis and antibiotic treatment and recovered, the heart r e t u r n i n g gradually to normal within nine m o n t h s (Fig. 6 D). W e believe that in this case the predominant radiological features on first examination were those of diffuse interstitial pneumonia, although a myocarditis was already present, the heart silhouette being slightly enlarged.
s e c o n d a r y to p n e u m o n i t i s was p r a c t i c a l l y i m p o s s i b l e : t h e s e 4 p a t i e n t s h a d p h y s i c a l s i g n s o f rfiles a n d h a r s h b r e a t h s o u n d s w i t h c h e s t films e q u a l l y s u g g e s t i v e o f i n f l a m m a t i o n or c o n g e s t i o n . " T h e cases in w h i c h t h e h i s t o p a t h o l o g i c a l e x a m i n a t i o n (Gellei a n d Griffel, 1958) s h o w e d i n t e r s t i t i a l i n f l a m m a t o r y i n f i l t r a t i o n o f t h e l u n g s are p r o o f t h a t t h e c o m b i n a t i o n o f p r i m a r y interstitial myocarditis with interstitial pneumonia ( p n e u m o n i t i s ) m u s t b e a relatively f r e q u e n t o c c u r r e n c e . T h i s w o u l d s u p p o r t t h e v i e w o f a viral o r i g i n
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of primary interstitial myocarditis. There were cases in which radiological evidence of perihilar cedema was present; only in one case was generalized pulmonary cedema seen. As mentioned before, 4 cases showed no radiological signs of passive pulmonary congestion and yet the children died a few hours after the X-ray examination as did those with a very marked pulmonary congestion (Case 7, Fig. 7).
Fig. 7.--Case 7. Generalized heart enlargement of Stage I I (myopathie configuration of the heart). N o radiologicaI signs of passive pulmonary congestion. M a r k e d e m p h y s e m a of the lungs. Bronchopneumonic foci are shown in right upper lobe as well as in apex of right lower lobe. T h e child died a few hours after the X - r a y examination. O n histopathological examination, evidence of interstitial myocarditis, m a r k e d congestion and cedema of lungs, bronchopneumonie foei, and slight interstitial inflammatory infiltration of the lungs.
This suggests that neither from the size or shape of the heart nor from the degree of pulmonary congestion can prognostic deductions be drawn. In the children who did not die within hours after the X-ray examination and in whom further radiological observation was thus possible, the signs of pulmonary congestion could be seen to disappear within a few days. In some of the children one to two relapses could be observed clinically as well as radiologically, the tachycardia being the first sign of the relapse, followed by the reappearance of all signs of pulmonary congestion (Case 4, Fig. 4; Case 8, Fig. 8). 3. P l e u r a l F l u i d . - - I n all but 5 cases pleural fluid was seen as a bandlike shadow along the lateral chest wall, sometimes unilateral, sometimes bilateral. This sign is well known (Holzmann, 1952; Schiifer, 1955) and can be explained by transudation into the pleural cavity. In 13 cases, in addition, small amounts of interlobar fluid were noted. There exists a discrepancy between the radiological and the autopsy findings. At autopsy in 6 cases only pleural fluid was found. There is, however, no other radiological explanation for these bandlike shadows along the lateral chest wall seen in all except five of the cases. 4. P u l s a t i o n s o f the H e a r t . - - O f the 33 cases 17 were screened in addition to films being taken. Of these, i6 showed very weakened or indistinguishable pulsations. It must, however, be borne in mind that to judge the amplitude of the pulsation may be very difficult because of the ever present tachycardia
OF
RADIOLOGISTS
(I50--2OO heart-beats per minute in the majority of cases). No relation could be established between the size of the heart and the amplitude of pulsations. Though the dilatation bf the heart may be of small degree (Stage I or II) and the heart-beat may be scarcely visible, there may on the other hand be very marked dilatation of the heart (Stage III) with pulsa. tion still distinguishable. An important sign of the beginning of recovery (under digitalis treatment) is the reappearance of visible pulsation, which becomes clearly distinguish. able with the diminishing pulse-rate. On the other hand, as has been mentioned, the recurrence of tachycardia was seen as the first sign of a relapse. DIFFERENTIAL DIAGNOSTIC CONSIDERATIONS 1. T h e most important task of the radiologist, according to our experience during the epidemic, is the differentiation between acute pulmonary inflammatory disease and primary interstitial myocarditis. This becomes apparent on reading the following sentences in the clinical study of Williams and others (1953): " T h e pattern of cardiac failure in young infants can be a confusing one unless encountered previously. Disturbed, rapid breathing, cyanosis, cold extremities, poor capillary circulation and tachycardia occur in both cardiac failure and severe respiratory tract infection, especially pneumonia. Failure to demonstrate cardiac enlargement is the most important reason for mistaking acute heart failure for pneumonia." T h e differentiation will be easy if definite radiological evidence of lobar or lobular pneumonia is present, relieving the anxiety of the physician as well as of the radiologist for those children who are brought into the hospital in this severe condition. It has to be borne in mind, however, that these pneumonias may also be associated with myocarditis caused by the same agent, which makes careful radiological examination of the heart in these cases essential (see also under 3). T h e task of the radiologist becomes very difficult and sometimes impossible in the differentiation between primary interstitial myocarditis and diffuse interstitial pneumonia (pneumonitis). As has been mentioned before, cases of the latter kind are rather common in Israel and several of them were seen in the X-ray Department during the epidemic. In such cases, the radiologist and the physician have to decide quickly because energetic cardiac treatment introduced immediately may save the life of a child suffering from myocarditis. The differential diagnostic features are as follows. In diffuse interstitial pneumonia one of the leading. signs is the marked emphysema due to expiratory impairment. T h e heart is small in most of the cases. T h e pathological interstitial pattern is usually limited to the paramediastinal region (along its whole length), leaving the peripheral (third) zone free. The latter zone is usually involved in passive pulmonary congestion due to heart failure in myocarditis. We have reviewed our cases of primary and secondary diffuse interstitial pneumonia and in none of them were Kerley's B lines seen. We consider the presence of these lines to be an important differential diagnostic sign, giving evidence of passive pulmonary congestion. T h e almost invariable
PRIMARY
INTERSTITIAL
MYOCARDITIS
20I
presence of costal or interlobar pleural fluid in heart failure due to myocarditis may be of help in the diagnosis. In our experience it is a very rare occurrence in interstitial pneumonias. In acute bronchiolitis in which the clinical signs may be as severe as in myocarditis, the heart is normal and the pathological pattern of the lungs differs markedly from passive congestion, showing a fine granular miliary pattern. In acute laryngo-tracheo-bronchitis marked emphysema due to expiratory impairment is present, together with inspiratory distress, seen on fluoroscopy as inspiratory widening of the heart shadow (Munk
congestion caused a pathological interstitial pattern reaching into its most peripheral distributions (third zone). Kerley's B lines were usually present. T h e only definite sign of inflammatory interstitial (bronchial) involvement of the lungs was the emphysema
A
B
C D A, Jan. 25, I 9 5 7 . H e a r t enlargement Stage I I . M a r k e d signs o f pulmonary passive congestion spreading into the m o s t peripheral part of the lungs (third zone). Evidence of costal and interlobar fluid. M a r k e d e m p h y s e m a of the lungs. B, T a k e n f r o m film of Jan. 25, showing the peripheral zone. C, Feb. 7. Decrease in size of heart. T h e pulmonary congestion as well as the e m p h y s e m a no longer shown D, .Feb I8. Eleven days later. Relapse: M a r k e d pulmonary congestion. T h e child died a few hours after this .N-ray examination. O n histopathologicaI examination, interstitial myocarditis, congestion of lungs, pleural fluid, bronchopnanmonie loci, and h m m o r r h a g e s . Sub-endocardial fibrosis in the subaortic region. Pericardial fluid.
Fig. 8.--Case 8.
and Lederer, I954). T h e heart is usually of normal size. However, the differential diagnosis becomes very complicated in cases of combined diffuse interstitial pneumonia and myocarditis. As has been shown, I I out of 27 patients with myocarditis who died in 1957 presented histopathological evidence of interstitial inflammation of the lungs, the interalveolar and interlobular septa as well as the peribronchial structures being mainly involved. We searched for radiological signs which would prove the presence of both conditions. T h e passive pulmonary I5
due to expiratory impairment, but when this was combined with an enlarged heart it suggested that, in addition to interstitial pneumonia, myocarditis was present. There may be, however, at the first examination, a barely noticeable enlargement of the heart and the pathological interstitial pattern suggestive of interstitial pneumonia (see Case 6), and only at the second examination a few days later does the heart enlargement become apparent. This shows that in some cases a definite radiological conclusion as to the presence of both conditions may be impossible on the first examination.
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2. T h e radiological differentiation between primary interstitial myocarditis and other forms of primary myocardial disease is ~very limited. This applies particularly to sub-endocardial fibro-elastosis which is usually seen in the X-ray department at the stage of cardiac failure, presenting all the clinical as well as radiological signs shown in primary interstitial myocarditis. As has been mentioned before, a large percentage of cases in our series of myocarditis showed histopathological evidence of sub-endocardial fibrosis, supporting the view of Rosenbaum and co-workers (i953) that "sub-endocardial sclerosis may not be primary in itself but rather a response of the tissues to some basic stimulus such as anoxia". This view of these authors is based on the fact that in primary interstitial myocarditis as well as in aberrant left coronary arteries and in medial necrosis of the coronary arteries endocardial thickening is a frequent finding. We have no experience with the latter two entities. According to Rosenbaum and co-workers in both these conditions a differential diagnostic feature is, in addition to clinical considerations, the absence of congestive failure. T h e same applies, according to these authors, to glycogen storage disease of the heart. 3. It is impossible to differentiate on radiological grounds between primary interstitial myocarditis and secondary myocarditis because the radiological features are the same. Saphir and others (I944), in 97 cases of myocarditis in children, found i case of postdiphtheritic inflammation of the myocardium, 4 patients with meningitis, 7 with poliomyelitis, 12 with bronchopneumonia, 3 with lobar pneumonia, 3 with nephritis, 5 with bacterial endocarditis, 7 with 'rheumatic type' myocarditis, 14 true cases of rheumatic myocarditis, 3 of isolated myocarditis, and 4 of myocarditis associated with tuberculosis. Apart from the pneumonias, as has been discussed before, the differentiation between these individual forms of secondary myocarditis will remain the task of the physician. T h e responsibility of the radiologist will be to confirm the clinically suspected myocarditis in the diseases mentioned. 4- Generalized heart enlargement with pulmonary congestion in decompensated rheumatic carditis may present the same radiological appearance 'as cardiac failure due to myocarditis. Here, too, the heart may be uniformly enlarged and the differentiation between the individual chambers may be impossible so that no signs pointing to a particular valvular involvement may be present. It still occurs, though rarely, that cases of rheumatic heart disease make their first appearance in the hospital and in the X-ray department at this advanced stage of the disease. It is well known, however, that rheumatic disease of the heart does not appear during the first year of life--in which so many of our cases of primary interstitial myocarditis occurred--and usually does not develop ~efore the fourth year of life. 5. Decompensated congenital cardiac disease may present a very difficult differential diagnostic problem, particularly in the second half of the first year of life, in which so many cases of primary interstitial myocarditis occur, and when the appearance of the heart does not offer any differentiating signs. T h e globular heart present in these conditions in infancy and early childhood offers few possibilities
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to evaluate the size of the pulmonary trunk which is so valuable a sign in older children and in adults. T h e radiological appearafice of the hilar and mid-zone branches of the pulmonary arteries may help in the differential diagnosis. T h e differentiation between passive pulmonary congestion due to mitral heart disease or left cardiac failure, and active arterial overflow due to an extra- or intracardial left-to-right shunt, is usually possible because of the differing appearance of the hilar and mid-zone branches of the pulmonary arteries. Well-defined, markedly dilated hilar and mid-zone arterial branches will point in favour of a left'to-right shunt. Pulsations of these arteries in infants and small children are, how. ever, difficult to observe. In the majority of our cases of myocarditis no marked enlargement of the hilar arteries (hilar shadows) was noted, the reason being that the heart failure develops suddenly and the engorgement of the bigger branches of the pulmonary arteries does not reach any marked degree. 6. As has been mentioned before, the radiological differentiation between primary interstitial myocarditis (Stage I I I of heart enlargement) and pericardial effusion (pericarditis) may be impossible from the appearance of the heart. In addition, decrease or disappearance of visible cardiac pulsations is noted in both. However, pulmonary passive congestion (left heart failure) is in our experience rarely seen in pericarditis, even with very extensive enlargement of the heart silhouette due to large amounts of pericardial fluid.
SUMMARY Th e radiological observations in 33 cases of primary interstitial myocarditis in the age-group 6 months to 3½ years are reported. T h e radiological features of the disease are presented. According to the size and shape of the heart, three stages of myopathic heart configuration are shown, presenting phases of the increasing myogenic dilatation of the heart. In cases that permitted further observation, gradual decrease of the size of the heart with eventual return to normal could be seen. T h e radiological appearances of passive pulmonary congestion, which were present in all but 4 cases, are discussed. Cases are presented with the typical appearances of arterial venous and lymphatic engorgement extending into the most peripheral parts of the lung fields (third zone) together with Kerley's B lines. In addition, cases are reported with a pathological interstitial pattern suggestive of diffuse interstitial pneumonia, these cases showing marked emphysema. T h e deduction is drawn that the combination of primary interstitial myocarditis with diffuse interstitial pneumonia must be a relatively frequent occurrence. This is supported by the fact that I I out of 27 patients who died in i957 showed on histopathological examination evidence of interstitial inflammatory infiltration of the lungs, in addition to interstitial myocarditis. Radiological evidence of pleural fluid was seen in 28 out of the 33 cases. Diminished or invisible cardiac pulsations may be of diagnostic aid. T h e radiological differential diagnostic considerations are discussed. T h e most important task of the radiologist is considered to be the differentiation between acute inflammatory pulmonary disease and
PRIMARY
INTERSTITIAL
myocarditis, the presenting severe clinical signs in both these conditions making a clinical differentiation sometimes very difficult. T h e differential diagnostic features between heart failure due to myocarditis and diffuse interstitial pneumonia are described, marked emphysema with a small heart and absence of Kerley's B lines pointing in favour of the latter. In addition the pathological interstitial pattern in diffuse interstitial pneumonia is usually limited to the paramediastinal regions (leaving the outer third free). T h e fine granular miliary pattern in acute bronchiolitis is thought to permit differentiation of this disease. T h e radiological signs of ~he combination of primary interstitial myocarditis with diffuse interstitial pneumonia are discussed, the most important feature being a marked emphysema and at the same time an enlarged heart. T h e differentiation from other forms of primary myocardial disease is mentioned; sub-endocardial fibro-elastosis offers no differentiating radiological signs. T h e radiological appearance of secondary myocarditis due t o diphtheria, poliomyelitis, meningitis, nephritis, bacterial endocarditis, etc., presents no radiological differential diagnostic features. T h e differential diagnostic considerations between myocarditis and decompensated rheumatic carditis as well as decompensated congenital cardiac disease are mentioned. An important differential diagnostic sign between primary interstitial myocarditis and pericardial effusion (pericarditis) is believed to be the rare or very late occurrence of left heart failure (passive pulmonary congestion) in the latter.
Acknowledgements.--Dr. J. Munk wishes to express his sincere thanks to Dr. Peter Kerley for the valuable knowledge gained at the X-ray Departments of the Westminster Hospital and of the National Heart Hospital in London. Much help was thus obtained in the writing of this paper. T h e authors wish to thank Dr. W. Falk and Dr. E. Freundlich of the Department of Pmdiatrics B, Dr. J. Bar-Hay and Dr. M. Berkowitz from the Department of P~ediatrics A, Rambam Government Hospital, Haifa, for their help and co-operation; Dr. B. Gellei and Dr. S. Griffel from the Department of Pathology, Rambam Government Hospital, Haifa, for their aid and valuable advice ; Dr. B. Ostrowsky, Dr. S. T. Winter, Dr. Z. Sehwarz, and Dr. W. Sh. Moses from the Rothschild Hospital, Haifa, for their kind permission to include their cases in this paper.
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Thanks are due to the medical staff of the X-ray Department of the Rambam Government Hospital, Haifa, Dr. A. Jungmann, Dr. L. Rolan, Dr. E. Hahn, and Dr. P. Boldo for their continued interest which made the publication of the paper possible. REFERENCES BRIGDEN,W. (I957), Lancet, 2, 1179, 1243. BRUW~R, A. J. (1956), Amer. J. Roentgenol., 76, 4CAFFEY, J. (I956), Pediatric X-ray Diagnosis. Chicago: The Yearbook Publishers. CHOREMIS, C., CASSIMOS, CH., 'NIKOYANNOPOULOS,J., MAVROU, K., and HAKA, C. (I956), Ann. Pediat., 187, 444. "\ EBNOTHER, C. L., and ABRAMS, H. L. (I957), "Amer. J. Roentgenol., 77, 2. EscH, D., and THURN, P. (I957), Fortschr. R6ntgenstr., 87, 7FIEDLER, A. (19oo), Zbl. inn. Med., 21, 212. Fr~UNDLICH, E., BERKOWlTZ, M., ELKON, A., and WILDER,A: (z958), Amer.J. Dis. Child., to be published. GELLEI,. B., and GRIEFEL, S. (1958), personal communication. HOLZMANN, M. (I952), Lehrbuch der R6ntgendiagnostik (ed. H. R. SCHINZ, W. E. BAENSCH, E. FRIEDL, and E. UEHEINGER), 5th ed., vol. 3, P. 2828. Stuttgart: G. Thieme. JAVETT, S. N., HEYMANN,$!/S.,MUNDEL, B., PEPLER, W. J., LURIE, H. J., GEAR, J., MEASROCK,V., and KIRSCH, Z. (I956), J. Pediat., 48, I. KERLEY, P. (I95I), Textbook of X - r a y Diagnosis (ed: S. C. SHANKSand P. KERLEY), 2nd ed., vol. 2, p. 405 . Philadelphia: Saunders. LIND, J., and HULTQUIST,G. T. (i949) , Amer. Heart ft., 38, z23. MONTGOMERY, J., GEAR, J., PRINSLOO, F. R., KAHN, M., and KIRSCH, Z. (I955), S. Afr. reed. J., 29, 608. MUNK, J., and LEDEmm, K. T. (I954), Brit. J. Radiol., 27, 294. ROSENBAUM, H. D., NADAS, A. S., and NEUHAUSER, E. B. D. (I953), Amer. J. Dis. Child., 86, 28. SAPHIR, O. (I942), Amer. HeartJ., 24, 167. - - - - WILE, S. A., and REINGOLD, I. M. (I944) , Amer. J. Dis. Child., 67, 294. SCHXEER, K. H. (I955), PfidiatriScher RSntgenatlas. Stuttgart: G. Thieme. STOEBER, E. (I952), Z. Kinderheilk., 71, 319, 592. TEDESCHI, C. G., and STEVENSON, T. D. (I95I), New EngL J. Med., 244, 352. VAN Cm~VELD, S., and JAGER, H. (I956), Ann. Pediat., 187, zoo. WILLIAMS, H., O'REILLY, R. N., and WILLIAMS,A. (I953) , Arch. Dis. Childh., 28, 14o. ZDANSKY, E. (I957), R6"ntgendiagnostik, Ergebnisse 19521956 (ed. H. R. SCHINZ, R. GLAUNER, and E. UEHLINGER), p. IO4. Stuttgart: G. Thieme. ZUPPINGER, H. (i9oi), Wien. klin. Wschr., 14, 799.